Information on EC 2.7.11.10 - IkappaB kinase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
2.7.11.10
-
RECOMMENDED NAME
GeneOntology No.
IkappaB kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + [IkappaB protein] = ADP + [IkappaB phosphoprotein]
show the reaction diagram
activation and reaction mechanism
-
ATP + [IkB protein] = ADP + [IkB phosphoprotein]
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
phospho group transfer
-
-
phospho group transfer
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:[IkappaB protein] phosphotransferase
The enzyme phosphorylates IkappaB proteins at specific serine residues, which marks them for destruction via the ubiquitination pathway. Subsequent degradation of the IkB complex (IKK) activates NF-kappaB, a translation factor that plays an important role in inflammation, immunity, cell proliferation and apoptosis. If the serine residues are replaced by threonine residues, the activity of the enzyme is decreased considerably.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
CHUK
Q60680
-
I kappa B kinase alpha
-
-
IkappaB alpha kinase
O14920
-
IkappaB kinase
-
-
IkappaB kinase
-
-
IkappaB kinase
-
-
IkappaB kinase alpha
-
-
IkappaB kinase alpha
O15111
-
IkappaB kinase alpha
-
-
IkappaB kinase alpha
Q60680
-
IkappaB kinase alpha
-
-
IkappaB kinase beta
-
-
IkappaB kinase beta
-
-
IkappaB kinase complex
-
-
IkappaB kinase epsilon
Q14164
-
IkappaB kinase-1
Q15111
-
IkappaB kinase-2
O14920
-
IkappaB kinase-2
-
-
IkappaB kinase-2
-
-
IkappaB kinase-alpha
-
-
IkappaB kinase-beta
-
-
IkappaB kinase-beta
-
-
IkappaB-kinase
-
-
IkappaBalpha
O15111
-
IkappaBalpha kinase
-
-
IkappaBbeta kinase
-
-
IKK
O15111
-
IKK
Mus musculus C57BI/6J
-
-
-
IKK beta
O14920
-
IKK complex
-
-
IKK complex
-
-
IKK-1
Q15111
-
IKK-alpha
-
-
IKK-beta
-
-
IKK-related kinase
-
-
IKK1
-
-
IKK2
-
-
Ikka
-
-
IKKalpha
Q60680
-
IKKalpha
Mus musculus BALB/c
-
-
-
IKKbeta
-
one of the catalytic subunits
IKKbeta
O88351
-
IKKbeta
Mus musculus BALB/c
-
-
-
IKKbeta
Q9QY78
-
IKKepsilon
-
-
IKKepsilon
Q14164
-
IKKi
-
-
inhibitor of kappaB kinase
-
-
inhibitor of nuclear factor kappa B kinase beta subunit
O88351
-
inhibitor of nuclear factor kappa B kinase beta subunit
Q9QY78
-
inhibitor of nuclear factor kappa B kinase beta subunit inhibitor of nuclear factor kappa-B kinase alpha subunit
O14920
-
inhibitor of nuclear factor kappa B kinase beta subunit inhibitor of nuclear factor kappa-B kinase alpha subunit
O15111
-
inhibitor of nuclear factor kappa-B kinase alpha subunit
Q60680
-
inhibitor of nuclear factor kappa-B kinase epsilon subunit
Q14164
-
inhibitor of nuclear factor kappa-B kinase epsilon subunit
Q9R0T8
-
inhibitor of nuclear factor kB kinase-related kinase
-
-
LRRK2 kinase
-
-
non-canonical IkappaBkinase epsilon
-
-
serine/threonine-protein kinase pkn1
P33973
-
TANK-binding kinase 1
-
-
TANK-binding kinase 1
A1L361
-
TBK1
-
-
TBK1
A1L361
-
TBK1 kinase
-
-
CAS REGISTRY NUMBER
COMMENTARY
159606-08-3
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
IkappaBalpha and IkappaBbeta
-
-
Manually annotated by BRENDA team
IKK-1 and IKK-2
-
-
Manually annotated by BRENDA team
IKK-alpha and IKK-beta
-
-
Manually annotated by BRENDA team
IKKepsilon is a noncanonical IkappaB kinase homologue
-
-
Manually annotated by BRENDA team
isozymes IKK1 and IKK2
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
Balb/c mice
-
-
Manually annotated by BRENDA team
BALB/cA Jcl-ny mice, BALB/cnu/nu mice, and NIKaly/aly mice
-
-
Manually annotated by BRENDA team
C57BI/6J mice
-
-
Manually annotated by BRENDA team
C57BL/6 wild-type mice or murine strains deficient in either subunits IKKalpha, IKKbeta, or IKKgamma, overview
-
-
Manually annotated by BRENDA team
gene Ikbke
-
-
Manually annotated by BRENDA team
IkappaBalpha and IkappaBbeta
-
-
Manually annotated by BRENDA team
IKK-alpha and IKK-beta
-
-
Manually annotated by BRENDA team
wild-type and IKKalpha- mice
-
-
Manually annotated by BRENDA team
Mus musculus BALB/c
Balb/c mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BI/6J
C57BI/6J mice
-
-
Manually annotated by BRENDA team
adult Sprague-Dawley rat
-
-
Manually annotated by BRENDA team
RH strain in mouse embryonic fibroblast host MEF cells, wild-type and IKKalpha- or IKKbeta-deficient host cells
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
different patterns of beta-catenin activation in IKKalpha- and IKKbeta-deficient mouse embryonic fibroblast cells
malfunction
-
suppression of NF-betaB activation by nimbolide is caused by inhibition of IkappaB kinase, which leads to suppression of IkappaBalpha phosphorylation and degradation, nuclear translocation, DNA binding, and gene transcription. Nimbolide suppresses TNF-alpha-induced tumor cell invasion and NF-kappaB activation in a not-cell-specific manner
metabolism
-
IKKbeta is involved in the mechanism of regulation of the p73 and p53 network via DELTANp73alpha protein stabilization and inhibition of p53-regulated gene expression
metabolism
-
in resting cells, NF-kappaB is kept in an inactive state in the cytoplasm as a heterotrimer consisting of p50, p65, and IkappaB proteins, including IkappaBalpha, IkappaBbeta, and IkappaBepsilon. In response to activation signals, the IkappaBalpha subunit is phosphorylated at serine residues 32 and 36 and ubiquitinated at lysine residues 21 and 22, which target them for proteasome-mediated degradation
metabolism
-
LRRK2 does not play a major role in regulating the secretion of inflammatory cytokines induced by activation of the MyD88 pathway and LRRK2 kinase activity is not required for TLR-mediated Ser935 phosphorylation
metabolism
-
TAK1-mediated IKKalpha activation may regulate IRF3-dependent IFNbeta expression downstream of IKKepsilon/TBK1 activation in dendritic cells. IKKalpha-mediated phosphorylation of IRF3 promotes CBP recruitment and transcriptional activity
metabolism
-
when cells receive appropriate stimuli, such as TNF-alpha, a ternary IKK complex consisting of IKKalpha, IKKbeta and NEMO (IKKgamma) induces IkappaB phosphorylation, leading to IkappaB ubiquitination and proteasomal degradation that are required for liberation of NF-kappaB in the nucleus where it binds to specific promoter elements to activate gene expression. Regulations of cell cycle progression by nuclear IKKalpha, and nuclear function of IKKalpha in tumorigenesis and metastasis, overview
physiological function
-
IkappaB kinase activates NF-kappaB which plays a pivotal role in pro-inflammatory response in the lung
physiological function
-
IkappaB kinase beta is a key upstream regulator of the NF-kappaB pathway
physiological function
-
IkappaB kinase is a central kinase for nuclear factor-kappaB activation
physiological function
-
IKK is a central regulator of NF-kappaB transcription factors
physiological function
-
IKK-2 plays a role in regulating NF-kappaB signaling
physiological function
-
IKKbeta is shown to play an essential role in the activation of NF-kappaB in response to TNF-alpha and other inflammatory stimuli
physiological function
-
the IkappaB kinase complex catalyses the phosphorylation of IkappaBalpha at Ser32 and Ser36, essential for signaling the subsequent ubiquination and protosomal degradation of IkappaBalpha, thus leaving the NF-kappaB free to translocate to the nucleus and activate pro-inflammatory gene transcription
physiological function
-
the IkappaB kinase complex is critical for the activation of the NF-kappaB pathway
physiological function
-
the IkappaB kinase complex is essential in transducing the signal-inducible activation of the transcription factor NF-kappaB in response to proinflammatory stimuli
physiological function
-
IKK catalyzes phosphorylation of LRRK2 at Ser910 and Ser935, the phosphorylation sites that regulate the binding of protein 14-3-3 to LRRK2. Phosphorylation of LRRK2 by IKKs plays in controlling macrophage biology. But increased phosphorylation of Ser910 and Ser935 induced by activation of the MyD88 pathway is insensitive to LRRK2 kinase inhibitors
physiological function
-
IKK-2 plays a central role in the overall NF-kappaB regulation
physiological function
-
IKKalpha is required in dendritic cells for priming antigen-specific protective CD4+ and CD8+ T-cells, and acquired immunity to the human pathogen Listeria monocytogenes, role for IKKalpha in regulation of IFN regulatory factor 3, IRF3, activity and the functional maturation of dendritic cells. IKKalpha plays reciprocal roles in innate and adaptive immunity, limiting non-specific inflammation while promoting acquired antigen-specific immunity. Requirement for IKKalpha in lymphotoxin beta signalling in radiation-resistant stromal cells
physiological function
-
IKKalpha is required in dendritic cells for priming antigen-specific T cells, role for IKKalpha in regulation of IFN regulatory factor 3, IRF3, activity and the functional maturation of dendritic cells. Phosphorylation of the Ser402/404/405 cluster of residues is important for IRF3 activation and IFNbeta expression in response to viral infection. IKKalpha plays reciprocal roles in innate and adaptive immunity, limiting non-specific inflammation while promoting acquired antigen-specific immunity. IKKalpha activation in the haematopoietic compartment is critical for acquired immunity to the facultative intracellular pathogen Listeria monocytogenes. Requirement for IKKalpha in lymphotoxin beta signalling in radiation-resistant stromal cells
physiological function
-
phosphorylation and degradation of IkappaBalpha is mediated by activated IKKalpha and IKKbeta in the canonical pathway of NF-kappaB. IkappaB kinase beta increases DELTANp73alpha protein stability independently of its ability to activate NF-kappaB. IKKbeta associates with and phosphorylates DELTANp73alpha protein at Ser422, leading to its accumulation in the nucleus, where it binds and represses several p53-regulated genes. IKKbeta and DELTANp73alpha protein cross talk in cancer-derived cell lines and primary cancers
physiological function
-
the IkappaB kinase complex is the master kinase for NF-kappaB activation, in addition to mediating NF-kappaB signaling by phosphorylating IkappaB proteins during inflammatory and immune responses, the activation of the IKK complex also responds to various stimuli to regulate diverse functions independently of NF-kappaB. IKKalpha and IKKbeta have distinct physiological and pathological roles, while IKKbeta is predominantly cytoplasmic, IKKalpha shuttles between the cytoplasm and the nucleus with nuclear-specific roles of IKKalpha. Nuclear IKKalpha regulates NF-kappaB-dependent gene transcription and inflammation, regulatory functions of NF-kappaB, detailed overview. beta-Catenin-dependent transcription is decreased by IKKbeta but increased by IKKalpha. Regulation of apoptosis by nuclear IKKalpha. Nuclear IKKalpha is essential for cell cycle arrest and differentiation of keratinocyte in the epidermis and the morphogenesis of skeletal and craniofacial morphogenesis
physiological function
-
the IkappaB kinase complex is the master kinase for NF-kappaB activation, in addition to mediating NF-kappaB signaling by phosphorylating IkappaB proteins during inflammatory and immune responses, the activation of the IKK complex also responds to various stimuli to regulate diverse functions independently of NF-kappaB. IKKalpha and IKKbeta have distinct physiological and pathological roles, while IKKbeta is predominantly cytoplasmic, IKKalpha shuttles between the cytoplasm and the nucleus with nuclear-specific roles of IKKalpha. Nuclear IKKalpha regulates NF-kappaB-dependent gene transcription and inflammation, regulatory functions of NF-kappaB, detailed overview. Regulation of apoptosis by nuclear IKKalpha. Nuclear IKKalpha phosphorylates p73 within its N-terminal region, which may protect p73 from ubiquitination and proteasomal degradation, indispensable role of IKKalpha in cisplatin sensitivity. Nuclear IKKalpha is essential for cell cycle arrest and differentiation of keratinocyte in the epidermis and the morphogenesis of skeletal and craniofacial morphogenesis. Function of TGFbeta-induced nuclear IKKalpha seems to counter its metastatic role in breast cancer cells
metabolism
-
when cells receive appropriate stimuli, such as TNF-alpha, a ternary IKK complex consisting of IKKalpha, IKKbeta and NEMO (IKKgamma) induces IkappaB phosphorylation, leading to IkappaB ubiquitination and proteasomal degradation that are required for liberation of NF-kappaB in the nucleus where it binds to specific promoter elements to activate gene expression. Regulations of cell cycle progression by nuclear IKKalpha, and nuclear function of IKKalpha in tumorigenesis and metastasis, overview
additional information
-
homology molecular model of the IKK-2 kinase domain, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
P33973
autophosphorylation at both Ser and Thr
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both Ser32 and Ser36, modifications that are required for targeted degradation of IkappaB-alpha via the ubiquitin-proteasome pathway
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection
-
-
-
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
O88351
the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection
-
-
-
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
P33973
the expression of pkn1 is developmentally regulated to start immediately before spore formation. The enzyme plays an important role in the onset of proper differentiation
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
phosphorylation of IkappaBs marks them out for destruction, thereby relieving their inhibitory effect on NF-kappaB
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
show the reaction diagram
-
phosphorylation at the C-terminus of Bcl by IKKbeta disrupts Bcl10/Malt1 association and Bcl10-mediated signaling
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
show the reaction diagram
-
phosphorylation at the C-terminus of Bcl by IKKbeta, inactive with a C-terminal 93 amino acid-deletion mutant of Bcl
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl10
show the reaction diagram
-
Bcl10 is phosphorylated by the NEMO/IKK complex, recombinant substrate GST-Bcl10 expressed in HEK-293T cells, degradation of Bcl
-
-
?
ATP + Bcl10
ADP + phosphorylated Bcl10
show the reaction diagram
-
negative regulatory activity of the IKK complex in Bcl10 degradation, which is part of the regulatory mechanisms that precisely control the response to antigens, overview
-
-
?
ATP + GST-IkappaBalpha
ADP + GST-IkappaBalpha phosphoprotein
show the reaction diagram
-
activity assay
-
-
?
ATP + IkappaB alpha
ADP + phosphorylated IkappaB alpha
show the reaction diagram
-
-
-
-
?
ATP + IkappaB protein
ADP + phosphorylated IkappaB
show the reaction diagram
-
the enzyme targets the inhibitory IkappaB protein tightly bound to the transcription factor NF-kappaB for proteasomal degradation and allows the freed NF-kappaB to enter the nucleus where it can be transactivate its target gene, IKKalpha is involved in inflammation in macrophages
-
-
?
ATP + IkappaB protein
ADP + IkappaB phosphoprotein
show the reaction diagram
-
-
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
-
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
a step in NF-kappaB activation, the IKK complex, composed of IKKalpha, IKKbeta, and NEMO/IKKgamma, is the convergence point for many diverse NFkappaB-activating stimuli including TNFalpha, LPS, and IL-1, overview, IKKbeta is the primary positive regulator of NFkappaB activity in inflammatory processes, is the molecular link between inflammation and cancer
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
degradation of IkappaBalpha
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
phosphorylation of IkappaBalpha at Ser32 and Ser36
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
recombinant GST-fusion substrate
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
phosphorylation at Ser-32 and Ser-36
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated-IkappaBalpha
show the reaction diagram
-
-
-
-
?
ATP + IkappaBbeta
ADP + phosphorylated IkappaBbeta
show the reaction diagram
-
phosphorylation of IkappaBalpha at Ser19 and Ser23
-
-
?
ATP + interferon regulatory factor 3
ADP + phosphorylated interferon regulatory factor 3
show the reaction diagram
-
-
-
-
?
ATP + KKKKERLLDDRHDSGLDSMKDEE
ADP + phosphorylated-KKKKERLLDDRHDSGLDSMKDEE
show the reaction diagram
-
IKK substrate peptide derived from IkappaBalpha sequence
-
-
?
ATP + NF-kappaB p65 subunit
ADP + phosphorylated NF-kappaB p65 subunit
show the reaction diagram
-
IKKalpha and IKKbeta phosphorylate NF-kappaB p65 subunit at Ser536
-
-
?
ATP + p65/RelA
ADP + phosphorylated p65/RelA
show the reaction diagram
-
-
-
-
?
ATP + protein p100
ADP + phosphorylated protein p100
show the reaction diagram
-
interaction with the NF-kappaB complex, required for the interaction with the NF-kappaB complex
-
-
?
ATP + protein p165
ADP + phosphorylated protein p165
show the reaction diagram
-
p65 is part of the IKKepsilon complex with p25, interaction with the NF-kappaB complex, required for the interaction with the NF-kappaB complex
-
-
?
ATP + STAT1 transcription factor
ADP + phosphorylated STAT1 transcription factor
show the reaction diagram
-
-
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
show the reaction diagram
-
IKKalpha is required for histone function regulation in the nucleus
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser10
-
-
?
ATP + [biotinylated IkappaBa peptide]
ADP + [biotinylated IkappaBa phosphopeptide]
show the reaction diagram
-
i.e. biotin-Gly-Leu-Lys-Lys-Glu-Arg-Leu-Leu-Asp-Asp-Arg-His-Asp-Ser32-Gly-Leu-Asp-Ser36-Met-Lys-Asp-Glu-Glu
-
-
?
ATP + [DELTANp73alpha protein]
ADP + [DELTANp73alpha phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser422 by IKKbeta, IKKbeta is inactive with S422A mutant substrate. DELTANp73alpha i a dominant negative inhibitor of p53 and p73
-
-
?
ATP + [GST-IkappaB protein]
ADP + [GST-IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [GST-IkappaBalpha protein]
ADP + [GST-IkappaBalpha phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [GST-IkappaBalpha1-54 protein]
ADP + [GST-IkappaBalpha1-54 phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [GST-IkappaBalpha1-54 protein]
ADP + [GST-IkappaBalpha1-54 phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [GST-IkappaBalpha1-54 protein]
ADP + [GST-IkappaBalpha1-54 phosphoprotein]
show the reaction diagram
-
recombinant substrate derived from mouse IkappaBalpha
-
-
?
ATP + [GST-IkappaBbeta protein]
ADP + [GST-IkappaBbeta phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
show the reaction diagram
-
histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser10 by IKK-alpha
-
-
?
ATP + [IFN regulatory factor 3 protein (380-427)]
ADP + [IFN regulatory factor 3 phosphoprotein (380-427)]
show the reaction diagram
-
the truncated mutant is a good substrate
-
-
?
ATP + [IFN regulatory factor 3 protein]
ADP + [IFN regulatory factor 3 phosphoprotein]
show the reaction diagram
-
IRF3 activation is triggered by IKKepsilon/TBK1-mediated phosphorylation on Ser396, phosphorylation on Ser396, and phosphorylation of Ser402/404/405 cluster in the C-terminal regulatory domain of IRF3 in vitro
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
Q15111
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
inhibition and degradation of IkappaB, an inhibitor of NF-kappaB retaining it in the cytoplasm, phosphorylation of IkappaB marks the protein for ubiquitination followed by degradation, activated NF-kappaB is translocated to the nucleus initiating signalling pathways, regulation mechanism, overview
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
inhibitor substrate is bound to NF-kappaB
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
parasite IKKalpha, localized in parasitophorous vacuole membrane, activates mouse' intracellular NF-kappaB in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
phosphorylation of IkappaB results in its proteolytic degradation
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
required for activation of NF-kappaB resulting in activation of signalling pathways
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
signalling step of IKK bound to NFkappaB for subsequent ubiquitination of IkappaB and proteolytic degradation
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
the enzyme is also active with a peptide derived from IkappaB protein spanning Ser32 and Ser36 which are phosphorylated
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
the IkappaBalpha subunit of NF-kappaB is phosphorylated at serine residues 32 and 36, phosphorylation at Ser32 and Ser36 catalyzed by IkappaBalpha kinase
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
enzyme is involved in activation of pro-inflammation signalling
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
parasite IKKalpha, localized in parasitophorous vacuole membrane, activates mouse' intracellular NF-kappaB through phosphorylation of host IkappaBalpha at Ser32 and Ser36 in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
IKKbeta-dependent phosphorylation and subsequent ubiquitin-dependent proteolytic degradation of IKKalpha, the 2 subunits have opposing function in NF-kappaB metabolism, overview
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser32 and Ser36
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
phosphorylation on Ser32 and Ser36
-
-
?
ATP + [IkappaBbeta protein]
ADP + [IkappaBbeta phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaBbeta protein]
ADP + [IkappaBbeta phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser19 and Ser23
-
-
?
ATP + [IRF3 protein]
ADP + [IRF3 phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser396 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [leucine-rich repeat kinase 2 protein]
ADP + [leucine-rich repeat kinase 2 phosphoprotein]
show the reaction diagram
-
catalyzed reaction of canonical IKKalpha and IKKbeta and IKK-related IKKepsilon and TBK1 kinase, phosphorylation of LRRK2 at Ser910 and Ser935 by IKKalpha and IKKbeta
-
-
?
ATP + [NFkappaB subunit p56]
ADP + [NFkappaB subunit p56]phosphate
show the reaction diagram
-
-, phosphorylation at serine residues, especially at S536, in the cytoplasm prior to NFkappaB p56 translocation to the nucleus
-
-
?
ATP + [optineurin protein]
ADP + [optineurin phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser177 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [p73 protein]
ADP + [p73 phosphoprotein]
show the reaction diagram
-
IKKalpha in the nucleus
-
-
?
ATP + [RelA/p65 protein]
ADP + [RelA/p65 phosphoprotein]
show the reaction diagram
-
-, phosphorylation on Ser536 of the transactivation domain, dependent on lipopolysaccharide-induction, but not on Akt or p65
-
-
?
ATP + [S386A IFN regulatory factor 3 protein]
ADP + [S386A IFN regulatory factor 3 phosphoprotein]
show the reaction diagram
-
the mutant substrate is equally phosphorylated as the wild-type IRF3
-
-
?
ATP + [S396A IFN regulatory factor 3 protein]
ADP + [S396A IFN regulatory factor 3 phosphoprotein]
show the reaction diagram
-
the mutant substrate is equally phosphorylated as the wild-type IRF3
-
-
?
ATP + [S402A/S404A/S405A IFN regulatory factor 3 protein]
ADP + [S402A/S404A/S405A IFN regulatory factor 3 phosphoprotein]
show the reaction diagram
-
low activity with the IRF3 mutant
-
-
?
additional information
?
-
-
activation of heterodimeric nuclear transcription factor NFkappaB is an essential step in inflammation, e.g. resulting in osteoarthritis, ulcerative colitis, asthma, and Crohn's disease, signalling step for phosphorylation, subsequent ubiquitination and proteolytic degradation of IkappaB, NFkappaB remains free after the reaction and is translocated to the nucleus, NFkappaB activation is also involved in development of diseases like cancer, gut ischemia-reperfusion, diabetes, or in transplant rejections, overview
-
-
-
additional information
?
-
-
activation of NFkappaB by the catalytic subunit IKKbeta is required for signaling via the NFkappaB pathway in acute and systemic inflammation and for tissue protection
-
-
-
additional information
?
-
-
defective ubiquination of the NF-kappaB essential modifier/IkappaB kinase-gamma complex leads to impaired cellular NFkappaB signalling and hypohidrotic ectodermal dysplasia with immunodeficiency HED-ID
-
-
-
additional information
?
-
-
enzyme is responsible for NFkappaB activation, specific inhibition of IkB kinase reduces hyperalgesia in inflammatory and neuropathic pain models in male Sprague-Dawley rats
-
-
-
additional information
?
-
-
IkappaB kinases are essential key regulators of the NFkappaB pathways in the tooth development acting as stimulators, overview
-
-
-
additional information
?
-
-
IKK activates and regulates NFkappaB important in intracellular signalling, overview
-
-
-
additional information
?
-
-
IKK activates NF-kappaB through action of TNFalpha playing an important role in subsequent signaling pathways involved in e.g. apoptosis/cell survival, cell proliferation, and inflammation
-
-
-
additional information
?
-
-
IKK activates NF-kappaB which initiates signaling pathways that play critical roles in a variety of physiological and pathological processes, e.g. promotion of cell survival inducing production of apoptosis inhibitors in normal and cancer cells, pathways overview, IKK/NF-kappaB links inflammation to cancer, regulation of IKK, overview
-
-
-
additional information
?
-
-
IKK activates TNFalpha-dependent signaling pathways inducing 5-fluoro-2'-deoxyuridine drug resistance in different cell lines, overview
-
-
-
additional information
?
-
-
IKK is involved in NF-kappaB activation, IkappaB kinase IKKbeta, but not IKKalpha, is a critical mediator of NF-kappaB-dependent osteoclast survival preventing TNFalpha-induced cell death, and is required for formation of fully functional bone-resorbing osteoclasts and for inflammation-induced bone loss
-
-
-
additional information
?
-
-
IKK is required for activation of NF-kappaB and subsequent signalling pathways
-
-
-
additional information
?
-
-
IKK is responsible for activation of NFkappaB, herpesvirus HSV-1 potently induces IkappaB kinase IKK causing persistent induction of NFkappaB resulting in transactivation of HIV-1-LTR-regulated genes and induction of HIV-1 replication in infected T-cells
-
-
-
additional information
?
-
-
IKK is responsible for NF-kappaB activation by inactivating its inhibitor IkappaB, different inflammation stimuli induce distinct IKK activity profiles, molecular mechanism, overview
-
-
-
additional information
?
-
-
IKK marks cytoplasmic NFkappaB inhibitors for proteolytic destruction playing a role in regulation of genetic cell cycle programs, IKK regulates nuclear translocation of transcription factor NFkappaB
-
-
-
additional information
?
-
-
IKKalpha, not IKKbeta, is required for epidermal regeneration, IkappaB kinases are essential key regulators of the canonical and noncanonical NFkappaB pathways important for the expression of a wide variety of genes that are involved in the control of immune and inflammatory response, and in the regulation of cellular proliferation and survival, mechanism, overview
-
-
-
additional information
?
-
-
IKKbeta is required for activation of NFkappaB, IKKbeta induces expression of epithelial sodium channel alphabetagamma-ENaC in cell surfaces
-
-
-
additional information
?
-
-
IKKbeta is required for regulation of NFkappaB activity and peripheral B cell survival and proliferation
-
-
-
additional information
?
-
-
IKKbeta regulates the translocation of NF-kappaB from cytoplasm to nucleus earmarking the transcription factor for polyubiquitination and proteasome-mediated degradation, the cytokine TNFalpha-induced T-loop-phosphorylated IKKbeta becomes monoubiquitinated at Lyk163 proximal to the T-loop, mechanism of post-translational crosstalk, overview
-
-
-
additional information
?
-
-
infection and genome insertion of human cytomegalovirus induces expression of the catalytic subunit IKK2 in the host cell which is required for viral induction of NF-kappaB activation and involved in viral replication and lytic cycle
-
-
-
additional information
?
-
-
parasite Toxoplasma gondii IKKalpha, localized in parasitophorous vacuole membrane, activates the host intracellular NF-kappaB in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
-
additional information
?
-
-
subunit IKKbeta controls the activation of NF-kappaB, important in inflammation, IKKalpha plays a role in lyphoid organogenesis and suppresses NF-kappaB activity by accelerating both the turnover of the NFkappaB subunits RelA and c-Rel, and their removal from pro-inflammatory gene promoters, inactivation of IKKalpha enhances inflammation and bacterial clearance in mice, overview
-
-
-
additional information
?
-
-
the IKK complex is responsible for NFkappaB regulation
-
-
-
additional information
?
-
-
the noncanonical IkappaB kinase homologue IKKepsilon, beneath TANK-binding kinase-1 TBK-1, is required for activation of transcription factor NFkappaB and of interferon regulatory factor 3 IRF3, regulation and interaction, overview
-
-
-
additional information
?
-
-
Vav-1 and IKKalpha subunit of IkappaB kinase functionally associate to induce NFkappaB activation in response to CD28 engagement
-
-
-
additional information
?
-
-
TNF-R1-activated IKKbeta phosphorylates IKKgamma and IKKalpha, autophosphorylation patterns involving K163 of IKKbeta, regulation, overview
-
-
-
additional information
?
-
-
activated IKK2 is responsible for induction of leucocyte infiltration in pancreatic acini, the mutant ICC2CA in pancreatic acinar cells increases tissue damage of secretagogue induced experimental pancreatitits, the enzyme is involved in the proinflammatory IKK/NF-kappaB pathway, overview
-
-
-
additional information
?
-
-
hypoxia alters the cellular pool of IKKalpha and IKKbeta, and activates NFkappaB through a pathway involving activation of IkappaB kinase-beta, IKKbeta, leading to phosphorylation-dependent degradation of IkappaBalpha and liberation of NFkappaB, overview, hypoxia-induced activation of the NFkappaB pathway is independent of HIF-1alpha, prolyl hydroxylase-1 negatively regulates IKKbeta
-
-
-
additional information
?
-
-
IkappaB kinase beta plays a critical role in metallothionein-1 expression and protection against arsenic toxicity, two signaling pathways appear to be important for modulating arsenic toxicity. First, the IKK-NF-kappaB pathway is crucial for maintaining cellular metallothionein-1 levels to counteract reactive oxygen species accumulation, and second, when this pathway fails, excessive reactive oxygen species leads to activation of the MKK4-JNK pathway, resulting in apoptosis
-
-
-
additional information
?
-
-
IkappaB kinase beta plays an essential role in remodeling Carma1-Bcl10-Malt1 complexes upon T cell activation, T cell receptor signaling to IkappaB kinase/NF-kappaB is controlled by PKCtheta-dependent activation of the Carma1, Bcl10, and Malt1 CBM complex, IKKbeta triggers the CBM complex formation and phosphorylation of Bcl by PMA/ionomycin or CD3/CD28, regulation, overview
-
-
-
additional information
?
-
-
IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9, but IKK-a is dispensable for a cytoplasmic RNA helicase RIG-I-dependent cytosolic pathway-induced production of IFN-alpha in MEF cells, overview
-
-
-
additional information
?
-
-
IKK is responsible for activation of NF-kappaB by initiating the degradation of the NF-kappaB inhibitor IkappaB, subunits IKKalpha and IKKgamma/NEMO, not IKKbeta, are required for reovirus-induced NF-kappaB activation and apoptosis, overview
-
-
-
additional information
?
-
-
IKK-beta inhibition in vivo leads to reduction of rhinovirus-induced expression of CXCL8, CCL5, and IL-6, the enzyme is important in regulation of the NF-kappaB signaling pathway, overview
-
-
-
additional information
?
-
-
IKK-related kinases tank-binding kinase 1 TBK1/IKKi and cullin-based ubiquitin ligases are involved in IFN regulatory factor-3, IRF-3, phosphorylation, activation, and degradation, IRF-3 activation is induced by viral infection, e.g. by HCMV, molecular mechanisms, detailed overview
-
-
-
additional information
?
-
-
IKKalpha and IKKbeta are distinctly involved in ERK1-dependent, but IkappaBalpha-P65- and p100-p52-independent, upregulation of MUC5AC mucin transcription in case of infection by Streptococcus pneumoniae, MUC5AC mucin induction also requires pneumolysin and TLR4-dependent MyD88-IRAK1-TRAF6 signaling, molecular mechanism, overview
-
-
-
additional information
?
-
-
IKKalpha enhances p73-mediated transactivation and pro-apoptotic functions in p53-deficient H1299 cells, stabilization of p73, but not of the antagonist p53, by nuclear IKKalpha mediates cisplatin-induced apoptosis, DNA damage-induced accumulation of both p53 and p73alpha is associated with the up-regulation of IKK-alpha and IKK-gamma, a functional interaction might exist between them in DNA damage-mediated apoptotic pathways
-
-
-
additional information
?
-
-
IKKalpha is involved in the noncanonical NF-kappaB activation pathway, and plays an essential role in thymic organogenesis required for the establishment of self-tolerance, overview
-
-
-
additional information
?
-
-
IKKalpha is not only a regulator of mammary epithelial proliferation, but is also an important contributor to ErbB2-induced oncogenesis, providing signals that maintain mammary tumor-initiating cells, IKKalpha activity is required for cyclin D1 induction and proliferation of lobuloalveolar epithelial cells, and is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells, overview
-
-
-
additional information
?
-
-
IKKbeta subunit of IKK complex is essential for the activation of NF-kappaB in response to various proinflammatory signals, Cys179 of IkappaB kinase beta plays a critical role in enzyme activation by promoting phosphorylation of activation loop serines, overview
-
-
-
additional information
?
-
-
IKKepsilon is important in the regulation of the alternative NF-kappaB activation pathway involving p52 and p65, IKKepsilon interacts with p52 and promotes transactivation via p65
-
-
-
additional information
?
-
-
IKKepsilon, i.e. IKKi, is implicated in virus induction of interferon-beta, IFNbeta, and development of immunity, IKKepsilon functions in a redundant role to its ubiquitous counterpart, TBK1, in the activation of IRF3 and IRF7 ex vivo, IKKe determines ISGF3 binding specificity, regulaiton, overview
-
-
-
additional information
?
-
-
mechanisms/pathways of activation and derepression of the IKK complex, regulation, detailed overview
-
-
-
additional information
?
-
-
the IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories, IKKalpha is involved in the regulation of histone H3 phosphorylation and acetylation at specific gene promoters in hippocampus in the NF-kappaB pathway, inhibition of IKKalpha regulation results in impairments in fear memory reconsolidation, mechanism, overview
-
-
-
additional information
?
-
-
IKKalpha interacts with p73
-
-
-
additional information
?
-
-
interaction analysis of IKKepsilon with NF-kappaB complex components/p25/p65 by immunoprecipitation and mass spectrometric analysis, overview
-
-
-
additional information
?
-
-
no activity with Rip2
-
-
-
additional information
?
-
-
the enzyme activity is included in a complex formed of the scaffold protein NF-kappaB essential modulator, i.e. NEMO or IKKgamma, and the Ikkalpha and IKKbeta kinases, overview
-
-
-
additional information
?
-
Mus musculus BALB/c
-
IKKalpha and IKKbeta are distinctly involved in ERK1-dependent, but IkappaBalpha-P65- and p100-p52-independent, upregulation of MUC5AC mucin transcription in case of infection by Streptococcus pneumoniae, MUC5AC mucin induction also requires pneumolysin and TLR4-dependent MyD88-IRAK1-TRAF6 signaling, molecular mechanism, overview
-
-
-
additional information
?
-
Mus musculus C57BI/6J
-
activation of NFkappaB by the catalytic subunit IKKbeta is required for signaling via the NFkappaB pathway in acute and systemic inflammation and for tissue protection
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both Ser32 and Ser36, modifications that are required for targeted degradation of IkappaB-alpha via the ubiquitin-proteasome pathway
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection
-
-
-
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
O88351
the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection
-
-
-
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
P33973
the expression of pkn1 is developmentally regulated to start immediately before spore formation. The enzyme plays an important role in the onset of proper differentiation
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
phosphorylation of IkappaBs marks them out for destruction, thereby relieving their inhibitory effect on NF-kappaB
-
-
?
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
-
phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
show the reaction diagram
-
phosphorylation at the C-terminus of Bcl by IKKbeta disrupts Bcl10/Malt1 association and Bcl10-mediated signaling
-
-
?
ATP + Bcl10
ADP + phosphorylated Bcl10
show the reaction diagram
-
negative regulatory activity of the IKK complex in Bcl10 degradation, which is part of the regulatory mechanisms that precisely control the response to antigens, overview
-
-
?
ATP + IkappaB protein
ADP + phosphorylated IkappaB
show the reaction diagram
-
the enzyme targets the inhibitory IkappaB protein tightly bound to the transcription factor NF-kappaB for proteasomal degradation and allows the freed NF-kappaB to enter the nucleus where it can be transactivate its target gene, IKKalpha is involved in inflammation in macrophages
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
-
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
a step in NF-kappaB activation, the IKK complex, composed of IKKalpha, IKKbeta, and NEMO/IKKgamma, is the convergence point for many diverse NFkappaB-activating stimuli including TNFalpha, LPS, and IL-1, overview, IKKbeta is the primary positive regulator of NFkappaB activity in inflammatory processes, is the molecular link between inflammation and cancer
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
show the reaction diagram
-
degradation of IkappaBalpha
-
-
?
ATP + protein p100
ADP + phosphorylated protein p100
show the reaction diagram
-
interaction with the NF-kappaB complex
-
-
?
ATP + protein p165
ADP + phosphorylated protein p165
show the reaction diagram
-
p65 is part of the IKKepsilon complex with p25, interaction with the NF-kappaB complex
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
show the reaction diagram
-
IKKalpha is required for histone function regulation in the nucleus
-
-
?
ATP + [GST-IkappaB protein]
ADP + [GST-IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [GST-IkappaBalpha protein]
ADP + [GST-IkappaBalpha phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
show the reaction diagram
-
histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression
-
-
?
ATP + [IFN regulatory factor 3 protein]
ADP + [IFN regulatory factor 3 phosphoprotein]
show the reaction diagram
-
IRF3 activation is triggered by IKKepsilon/TBK1-mediated phosphorylation on Ser396
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
Q15111
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
inhibition and degradation of IkappaB, an inhibitor of NF-kappaB retaining it in the cytoplasm, phosphorylation of IkappaB marks the protein for ubiquitination followed by degradation, activated NF-kappaB is translocated to the nucleus initiating signalling pathways, regulation mechanism, overview
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
inhibitor substrate is bound to NF-kappaB
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
parasite IKKalpha, localized in parasitophorous vacuole membrane, activates mouse' intracellular NF-kappaB in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
phosphorylation of IkappaB results in its proteolytic degradation
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
required for activation of NF-kappaB resulting in activation of signalling pathways
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
signalling step of IKK bound to NFkappaB for subsequent ubiquitination of IkappaB and proteolytic degradation
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
show the reaction diagram
-
the IkappaBalpha subunit of NF-kappaB is phosphorylated at serine residues 32 and 36
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
enzyme is involved in activation of pro-inflammation signalling
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
show the reaction diagram
-
parasite IKKalpha, localized in parasitophorous vacuole membrane, activates mouse' intracellular NF-kappaB through phosphorylation of host IkappaBalpha at Ser32 and Ser36 in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
?
ATP + [IkappaBbeta protein]
ADP + [IkappaBbeta phosphoprotein]
show the reaction diagram
-
-
-
-
?
ATP + [IRF3 protein]
ADP + [IRF3 phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser396 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [leucine-rich repeat kinase 2 protein]
ADP + [leucine-rich repeat kinase 2 phosphoprotein]
show the reaction diagram
-
catalyzed reaction of canonical IKKalpha and IKKbeta and IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [NFkappaB subunit p56]
ADP + [NFkappaB subunit p56]phosphate
show the reaction diagram
-
-
-
-
?
ATP + [optineurin protein]
ADP + [optineurin phosphoprotein]
show the reaction diagram
-
phosphorylation at Ser177 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [p73 protein]
ADP + [p73 phosphoprotein]
show the reaction diagram
-
IKKalpha in the nucleus
-
-
?
ATP + [RelA/p65 protein]
ADP + [RelA/p65 phosphoprotein]
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
activation of heterodimeric nuclear transcription factor NFkappaB is an essential step in inflammation, e.g. resulting in osteoarthritis, ulcerative colitis, asthma, and Crohn's disease, signalling step for phosphorylation, subsequent ubiquitination and proteolytic degradation of IkappaB, NFkappaB remains free after the reaction and is translocated to the nucleus, NFkappaB activation is also involved in development of diseases like cancer, gut ischemia-reperfusion, diabetes, or in transplant rejections, overview
-
-
-
additional information
?
-
-
activation of NFkappaB by the catalytic subunit IKKbeta is required for signaling via the NFkappaB pathway in acute and systemic inflammation and for tissue protection
-
-
-
additional information
?
-
-
defective ubiquination of the NF-kappaB essential modifier/IkappaB kinase-gamma complex leads to impaired cellular NFkappaB signalling and hypohidrotic ectodermal dysplasia with immunodeficiency HED-ID
-
-
-
additional information
?
-
-
enzyme is responsible for NFkappaB activation, specific inhibition of IkB kinase reduces hyperalgesia in inflammatory and neuropathic pain models in male Sprague-Dawley rats
-
-
-
additional information
?
-
-
IkappaB kinases are essential key regulators of the NFkappaB pathways in the tooth development acting as stimulators, overview
-
-
-
additional information
?
-
-
IKK activates and regulates NFkappaB important in intracellular signalling, overview
-
-
-
additional information
?
-
-
IKK activates NF-kappaB through action of TNFalpha playing an important role in subsequent signaling pathways involved in e.g. apoptosis/cell survival, cell proliferation, and inflammation
-
-
-
additional information
?
-
-
IKK activates NF-kappaB which initiates signaling pathways that play critical roles in a variety of physiological and pathological processes, e.g. promotion of cell survival inducing production of apoptosis inhibitors in normal and cancer cells, pathways overview, IKK/NF-kappaB links inflammation to cancer, regulation of IKK, overview
-
-
-
additional information
?
-
-
IKK activates TNFalpha-dependent signaling pathways inducing 5-fluoro-2'-deoxyuridine drug resistance in different cell lines, overview
-
-
-
additional information
?
-
-
IKK is involved in NF-kappaB activation, IkappaB kinase IKKbeta, but not IKKalpha, is a critical mediator of NF-kappaB-dependent osteoclast survival preventing TNFalpha-induced cell death, and is required for formation of fully functional bone-resorbing osteoclasts and for inflammation-induced bone loss
-
-
-
additional information
?
-
-
IKK is required for activation of NF-kappaB and subsequent signalling pathways
-
-
-
additional information
?
-
-
IKK is responsible for activation of NFkappaB, herpesvirus HSV-1 potently induces IkappaB kinase IKK causing persistent induction of NFkappaB resulting in transactivation of HIV-1-LTR-regulated genes and induction of HIV-1 replication in infected T-cells
-
-
-
additional information
?
-
-
IKK is responsible for NF-kappaB activation by inactivating its inhibitor IkappaB, different inflammation stimuli induce distinct IKK activity profiles, molecular mechanism, overview
-
-
-
additional information
?
-
-
IKK marks cytoplasmic NFkappaB inhibitors for proteolytic destruction playing a role in regulation of genetic cell cycle programs, IKK regulates nuclear translocation of transcription factor NFkappaB
-
-
-
additional information
?
-
-
IKKalpha, not IKKbeta, is required for epidermal regeneration, IkappaB kinases are essential key regulators of the canonical and noncanonical NFkappaB pathways important for the expression of a wide variety of genes that are involved in the control of immune and inflammatory response, and in the regulation of cellular proliferation and survival, mechanism, overview
-
-
-
additional information
?
-
-
IKKbeta is required for activation of NFkappaB, IKKbeta induces expression of epithelial sodium channel alphabetagamma-ENaC in cell surfaces
-
-
-
additional information
?
-
-
IKKbeta is required for regulation of NFkappaB activity and peripheral B cell survival and proliferation
-
-
-
additional information
?
-
-
IKKbeta regulates the translocation of NF-kappaB from cytoplasm to nucleus earmarking the transcription factor for polyubiquitination and proteasome-mediated degradation, the cytokine TNFalpha-induced T-loop-phosphorylated IKKbeta becomes monoubiquitinated at Lyk163 proximal to the T-loop, mechanism of post-translational crosstalk, overview
-
-
-
additional information
?
-
-
infection and genome insertion of human cytomegalovirus induces expression of the catalytic subunit IKK2 in the host cell which is required for viral induction of NF-kappaB activation and involved in viral replication and lytic cycle
-
-
-
additional information
?
-
-
parasite Toxoplasma gondii IKKalpha, localized in parasitophorous vacuole membrane, activates the host intracellular NF-kappaB in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
-
additional information
?
-
-
subunit IKKbeta controls the activation of NF-kappaB, important in inflammation, IKKalpha plays a role in lyphoid organogenesis and suppresses NF-kappaB activity by accelerating both the turnover of the NFkappaB subunits RelA and c-Rel, and their removal from pro-inflammatory gene promoters, inactivation of IKKalpha enhances inflammation and bacterial clearance in mice, overview
-
-
-
additional information
?
-
-
the IKK complex is responsible for NFkappaB regulation
-
-
-
additional information
?
-
-
the noncanonical IkappaB kinase homologue IKKepsilon, beneath TANK-binding kinase-1 TBK-1, is required for activation of transcription factor NFkappaB and of interferon regulatory factor 3 IRF3, regulation and interaction, overview
-
-
-
additional information
?
-
-
Vav-1 and IKKalpha subunit of IkappaB kinase functionally associate to induce NFkappaB activation in response to CD28 engagement
-
-
-
additional information
?
-
-
activated IKK2 is responsible for induction of leucocyte infiltration in pancreatic acini, the mutant ICC2CA in pancreatic acinar cells increases tissue damage of secretagogue induced experimental pancreatitits, the enzyme is involved in the proinflammatory IKK/NF-kappaB pathway, overview
-
-
-
additional information
?
-
-
hypoxia alters the cellular pool of IKKalpha and IKKbeta, and activates NFkappaB through a pathway involving activation of IkappaB kinase-beta, IKKbeta, leading to phosphorylation-dependent degradation of IkappaBalpha and liberation of NFkappaB, overview, hypoxia-induced activation of the NFkappaB pathway is independent of HIF-1alpha, prolyl hydroxylase-1 negatively regulates IKKbeta
-
-
-
additional information
?
-
-
IkappaB kinase beta plays a critical role in metallothionein-1 expression and protection against arsenic toxicity, two signaling pathways appear to be important for modulating arsenic toxicity. First, the IKK-NF-kappaB pathway is crucial for maintaining cellular metallothionein-1 levels to counteract reactive oxygen species accumulation, and second, when this pathway fails, excessive reactive oxygen species leads to activation of the MKK4-JNK pathway, resulting in apoptosis
-
-
-
additional information
?
-
-
IkappaB kinase beta plays an essential role in remodeling Carma1-Bcl10-Malt1 complexes upon T cell activation, T cell receptor signaling to IkappaB kinase/NF-kappaB is controlled by PKCtheta-dependent activation of the Carma1, Bcl10, and Malt1 CBM complex, IKKbeta triggers the CBM complex formation and phosphorylation of Bcl by PMA/ionomycin or CD3/CD28, regulation, overview
-
-
-
additional information
?
-
-
IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9, but IKK-a is dispensable for a cytoplasmic RNA helicase RIG-I-dependent cytosolic pathway-induced production of IFN-alpha in MEF cells, overview
-
-
-
additional information
?
-
-
IKK is responsible for activation of NF-kappaB by initiating the degradation of the NF-kappaB inhibitor IkappaB, subunits IKKalpha and IKKgamma/NEMO, not IKKbeta, are required for reovirus-induced NF-kappaB activation and apoptosis, overview
-
-
-
additional information
?
-
-
IKK-beta inhibition in vivo leads to reduction of rhinovirus-induced expression of CXCL8, CCL5, and IL-6, the enzyme is important in regulation of the NF-kappaB signaling pathway, overview
-
-
-
additional information
?
-
-
IKK-related kinases tank-binding kinase 1 TBK1/IKKi and cullin-based ubiquitin ligases are involved in IFN regulatory factor-3, IRF-3, phosphorylation, activation, and degradation, IRF-3 activation is induced by viral infection, e.g. by HCMV, molecular mechanisms, detailed overview
-
-
-
additional information
?
-
-
IKKalpha and IKKbeta are distinctly involved in ERK1-dependent, but IkappaBalpha-P65- and p100-p52-independent, upregulation of MUC5AC mucin transcription in case of infection by Streptococcus pneumoniae, MUC5AC mucin induction also requires pneumolysin and TLR4-dependent MyD88-IRAK1-TRAF6 signaling, molecular mechanism, overview
-
-
-
additional information
?
-
-
IKKalpha enhances p73-mediated transactivation and pro-apoptotic functions in p53-deficient H1299 cells, stabilization of p73, but not of the antagonist p53, by nuclear IKKalpha mediates cisplatin-induced apoptosis, DNA damage-induced accumulation of both p53 and p73alpha is associated with the up-regulation of IKK-alpha and IKK-gamma, a functional interaction might exist between them in DNA damage-mediated apoptotic pathways
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-
-
additional information
?
-
-
IKKalpha is involved in the noncanonical NF-kappaB activation pathway, and plays an essential role in thymic organogenesis required for the establishment of self-tolerance, overview
-
-
-
additional information
?
-
-
IKKalpha is not only a regulator of mammary epithelial proliferation, but is also an important contributor to ErbB2-induced oncogenesis, providing signals that maintain mammary tumor-initiating cells, IKKalpha activity is required for cyclin D1 induction and proliferation of lobuloalveolar epithelial cells, and is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells, overview
-
-
-
additional information
?
-
-
IKKbeta subunit of IKK complex is essential for the activation of NF-kappaB in response to various proinflammatory signals, Cys179 of IkappaB kinase beta plays a critical role in enzyme activation by promoting phosphorylation of activation loop serines, overview
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-
-
additional information
?
-
-
IKKepsilon is important in the regulation of the alternative NF-kappaB activation pathway involving p52 and p65, IKKepsilon interacts with p52 and promotes transactivation via p65
-
-
-
additional information
?
-
-
IKKepsilon, i.e. IKKi, is implicated in virus induction of interferon-beta, IFNbeta, and development of immunity, IKKepsilon functions in a redundant role to its ubiquitous counterpart, TBK1, in the activation of IRF3 and IRF7 ex vivo, IKKe determines ISGF3 binding specificity, regulaiton, overview
-
-
-
additional information
?
-
-
mechanisms/pathways of activation and derepression of the IKK complex, regulation, detailed overview
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-
-
additional information
?
-
-
the IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories, IKKalpha is involved in the regulation of histone H3 phosphorylation and acetylation at specific gene promoters in hippocampus in the NF-kappaB pathway, inhibition of IKKalpha regulation results in impairments in fear memory reconsolidation, mechanism, overview
-
-
-
additional information
?
-
Mus musculus BALB/c
-
IKKalpha and IKKbeta are distinctly involved in ERK1-dependent, but IkappaBalpha-P65- and p100-p52-independent, upregulation of MUC5AC mucin transcription in case of infection by Streptococcus pneumoniae, MUC5AC mucin induction also requires pneumolysin and TLR4-dependent MyD88-IRAK1-TRAF6 signaling, molecular mechanism, overview
-
-
-
additional information
?
-
Mus musculus C57BI/6J
-
activation of NFkappaB by the catalytic subunit IKKbeta is required for signaling via the NFkappaB pathway in acute and systemic inflammation and for tissue protection
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
required
Mg2+
-
required
Mn2+
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)phenyl)acetic acid
-
IC50 for the IKKbeta is 0.0022 mM
(E)-4-[3-(5-(adamant-1-yl)-2-(but-1-oxy)-4-(2-methoxyethoxymethoxy)-phenyl)-3-oxoprop-1-en-1-yl]benzoic acid
-
shows highest inhibition of IKKbeta and highest induction of apoptosis in Jurkat cells
(E)-4-[3-(5-(adamant-1-yl)-2-(hexyl-1-oxy)-4-(2-methoxyethoxymethoxy)phenyl)-3-oxoprop-1-en-1-yl]benzoic acid
-
exhibits improved anti-IKKbeta and growth inhibitory activities and has lost its RAR-dependent transactivation function
(E)-4-[3-(5-(adamant-1-yl)-2-ethoxy-4-(2-methoxyethoxymethoxy)phenyl)-3-oxoprop-1-en-1-yl]benzoic acid
-
-
(E)-4-[3-(5-(adamant-1-yl)-4-(2-methoxyethoxymethoxy)-2-(pentyl-1-oxy)phenyl)-3-oxoprop-1-en-1-yl]benzoic acid
-
-
(E)-4-[3-(5-(adamant-1-yl)-4-(2-methoxyethoxymethoxy)-2-(prop-2-en-1-oxy)phenyl)-3-oxoprop-1-en-1-yl]benzoic acid
-
-
(E)-4-[3-(5-(adamant-1-yl)-4-(2-methoxyethoxymethoxy)-2-(prop-2-yn-1-oxy)phenyl)-3-oxoprop-1-en-1-yl]benzoic acid
-
shows highest inhibition of IKKbeta and highest induction of apoptosis in Jurkat cells
(E)-4-[3-(5-(adamant-1-yl)-4-(2-methoxyethoxymethoxy)-2-phenylmethoxy-phenyl)-3-oxoprop-1-en-1-yl]benzoic acid
-
exhibits improved anti-IKKbeta and growth inhibitory activities and has lost its RAR-dependent transactivation function
(E)-4-[3-(5-adamant-1-yl-4-(2-methoxyethoxymethoxy)-2-(prop-1-oxy)-phenyl)-3-oxoprop-1-en-1-yl]benzoic acid
-
-
1-(4-chlorophenyl)-4-ureido-1H-pyrazole-3-carboxamide
-
i.e. SC-108
1-(6-chloro-9H-beta-carbolin-8-yl)-3-methylurea
-
inhibits IKK with IC50 of 0.02 mM
1-(benzo[d][1,3]dioxol-5-yl)-8-(3-chloroisonicotinamido)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
-
i.e. PHA-379
1-(benzo[d][1,3]dioxol-5-yl)-8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-4,5-dihydro-1H-benzo-[g]indazole-3-carboxamide
-
i.e. PHA-250
1-[3-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanamine
-
-
1-[4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanamine
-
-
1-[4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanesulfonamide
-
-
15d-prostaglandin J2
-
strongly inhibits IKK
17-acetoxyjolkinolide B
-
17-AJB is isolated from a traditional Chinese medicinal herb Euphorbia fischeriana Steud. 17-AJB interacts with IKK directly and keeps IKK in its phosphorylated form irreversibly, inactivating its kinase activity, leading to its failure to activate NF-kappaB. The effect of 17-AJB on IKK is specific. It has no effect on other kinases such as p38, p44/42, and JNK. 17-AJB induces apoptosis in tumor cells
2-(4-fluorophenyl)-8-methyl-N-[2-(piperidin-1-yl)ethyl]-8H-imidazo[4,5-d][1,3]thiazolo[5,4-b]pyridin-5-amine
-
-
2-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzoic acid
-
IC50 for the IKK complex is above 0.1 mM
2-amino-6-(2-hydroxy-6-isobutoxyphenyl)-4-(piperidin-3-yl)nicotinonitrile
-
i.e. PHA-535E
2-benzamido-pyrimidines
-
diverse derivatives, synthesis and inhibitory potential determination, overview
2-hydroxy-N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]acetamide
-
-
2-methanesulfonyl-4-methyl-7-methylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7yl)pyridin-2-yl)methyl)acetamide
-
BMS-066, inhibitor of IKKbeta
3-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzoic acid
-
IC50 for the IKKbeta is 0.001 mM
3-amino-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-(1-benzofuran-2-yl)-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-(2-methoxyethoxy)thieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-(4-chlorophenyl)-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-(4-hydroxyphenyl)-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-ethoxythieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-furan-2-yl-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-methoxythieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-methyl-6-morpholin-4-ylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-methyl-6-piperazin-1-ylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-methyl-6-piperidin-1-ylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-4-propoxythieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(1,4-diazepan-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(2-aminoethoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(2-hydroxyethoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(3-aminoazepan-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(3-aminopropoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(3-hydroxypiperidin-1-yl)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(3-hydroxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(3-hydroxypropoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(3-oxo-1,4-diazepan-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(3-oxopiperazin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(4-aminopiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(4-carbamoylpiperazin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(4-carbamoylpiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(4-hydroxy-3,3-dimethylpiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(4-hydroxypiperidin-1-yl)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(4-hydroxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(4-methoxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-(4-methylpiperazin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-methyl-4-(2-methylpropyl)thieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-methyl-4-(4-methylphenyl)thieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-methyl-4-phenylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-methyl-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-methyl-4-pyridin-2-ylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-methyl-4-thiophen-2-ylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-methyl-4-[4-(methylsulfonyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-piperazin-1-yl-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-[(2-hydroxyethyl)amino]-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-[(3R)-3-aminopyrrolidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-[(3R)-3-hydroxypyrrolidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-[(3S)-3-aminopyrrolidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-[(3S)-3-hydroxypyrrolidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-[4-(dimethylamino)piperidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-[4-(methylamino)piperidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-amino-6-[4-[(methylsulfonyl)amino]piperidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
-
3-methoxy-N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]propanamide
-
;
3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzonitrile
-
-
3-[7-(benzyloxy)isoquinolin-6-yl]benzenesulfonamide
-
-
3-[7-(piperidin-4-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
-
4'-amino-4-chloro-4''-sulfamoyl-1,1':3',1''-terphenyl-5'-carboxamide
-
-
4,8-dimethoxy-1-vinyl-beta-carboline
-
i.e. beta-carboline alkaloid C-1, isolated from Melia azedarach var. japonica, inhibits IKK activity by reduction of IKK phosphorylation and degradation, and activation and nuclear translocation of NF-kappaB and subsequent signalling pathways
4-(1-benzothiophen-2-yl)-N-[3-chloro-4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 250 nM
4-(1-benzothiophen-2-yl)-N-[3-methoxy-4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 150 nM
4-(1-benzothiophen-2-yl)-N-[4-(pyrrolidin-1-ylcarbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 0.0085 mM, cellular profile
4-(1-benzothiophen-2-yl)-N-[4-([4-(dimethyl-amino)piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 80 nM, cellular profile
4-(1-benzothiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 70 nM, cellular profile
4-(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline
-
BMS-345541, inhibitor of IKKbeta
4-(5-(3-acetamino-3-methylbutyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 800 nM
4-(5-(3-amino-3-ethylpentyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 30 nM
4-(5-(3-amino-3-methyl-but-1-ynyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 200 nM
4-(5-(3-amino-3-methyl-butyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 40 nM
4-(5-(3-hydroxy-3-methylbutyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amin
-
IC50 for the IKK complex is 50 nM, cellular profile
4-(5-(3-methoxypropyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 100 nM, cellular profile
4-(5-(4-hydroxybutyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 40 nM, cellular profile
4-(7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]isoquinolin-6-yl)benzenesulfonamide
-
-
4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzoic acid
-
IC50 for the IKK complex is 0.018 mM, cellular profile
4-methyl-7-methylamino-2-(azepan-1-yl)-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-(methylthio)-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-benzylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-cyclopentylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-diethylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-ethylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-hydroxyethylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-methylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-methylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-piperidine-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-thienylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-methyl-7-methylamino-2-[1,2,3,6-tetrahydropyridine]-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
-
4-[7-(benzyloxy)isoquinolin-6-yl]benzenesulfonamide
-
-
4-[7-(piperidin-3-ylmethoxy)isoquinolin-6-yl]benzenesulfonamide
-
-
4-[7-(piperidin-3-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
-
4-[7-(piperidin-4-ylmethoxy)isoquinolin-6-yl]benzenesulfonamide
-
-
4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
-
4-[7-[(1-acetylpiperidin-4-yl)oxy]isoquinolin-6-yl]benzenesulfonamide
-
-
5,6-dibromo-beta-carboline
-
inhibits IKK with IC50 of 600 nM
5-((3-fluorophenyl)ethynyl)-2-ureidothiophene-3-carboxamide
-
i.e. PHA-966
5-(4-fluorophenyl)-2-ureidothiophene-3-carboxamide
-
i.e. SC-440
5-amino-2,30-bithiophene-4-carboxamide
-
i.e. SC-514
5-Aminosalicylate
-
weak inhibition of IKK-2
5-bromo-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 600 nM
5-bromo-6-cyano-beta-carboline
-
inhibits IKK with IC50 of 0.0011 mM
5-bromo-6-fluoro-beta-carboline
-
inhibits IKK with IC50 of 0.002 mM
5-bromo-6-methoxy-beta-carboline
-
nonspecific inhibitor of IKK, inhibits IKK with IC50 of 0.004 mM
5-bromo-6-trifluoromethyl-beta-carboline
-
inhibits IKK with IC50 of 0.0011 mM
5-bromo-beta-carboline
-
inhibits IKK with IC50 of 0.015 mM
6,8-dichloro-7-(cyclohexylmethoxy)-9H-beta-carboline
-
inhibits IKK with IC50 of 0.003 mM
6,8-dichloro-7-ethoxy-9H-beta-carboline
-
inhibits IKK with IC50 of 140 nM
6,8-dichloro-7-methoxy-9H-beta-carboline
-
inhibits IKK with IC50 of 170 nM
6,8-dichloro-9H-beta-carbolin-7-yl morpholine-4-carboxylate
-
inhibits IKK with IC50 of 0.0032 mM
6,8-dichloro-beta-carboline
-
inhibits IKK with IC50 of 200 nM
-
6-bromo-7-(piperidin-4-yloxy)isoquinoline
-
-
6-bromo-7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]isoquinoline
-
-
6-phenyl-7-(piperidin-3-ylmethoxy)isoquinoline
-
-
6-phenyl-7-(piperidin-3-yloxy)isoquinoline
-
-
6-phenyl-7-(piperidin-4-ylmethoxy)isoquinoline
-
-
6-phenyl-7-(piperidin-4-yloxy)isoquinoline
-
-
6-phenyl-7-(pyridin-3-ylmethoxy)isoquinoline
-
-
6-phenyl-7-(pyridin-4-ylmethoxy)isoquinoline
-
-
7-(2-fluorophenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
7-(3-fluorophenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
7-(3-methoxyphenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
7-(4-fluorophenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
;
7-(OCH2CH(CH2CH2))-6,8-dichloro-beta-carboline
-
inhibits IKK with IC50 of 80 nM
-
7-(piperidin-4-yloxy)isoquinoline
-
-
7-hydroxy-6,8-dichloro-beta-carboline
-
inhibits IKK with IC50 of 0.011 mM
-
7-[(1-acetylpiperidin-4-yl)oxy]-6-bromoisoquinoline
-
-
7-[(1-acetylpiperidin-4-yl)oxy]-6-phenylisoquinoline
-
-
7-[3-(aminomethyl)phenyl]-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
7-[[1-(ethylsulfonyl)piperidin-4-yl]methoxy]-6-phenylisoquinoline
-
-
7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]-6-phenylisoquinoline
-
-
8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
-
PHA-408, ATP-competitive, selective IKK-2 inhibitor; PHA-408, ATP-competitive, selective IKK-2 inhibitor
8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
-
PHA-408, ATP-competitive, selective IKK-2 inhibitor
8-amino-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 0.0013 mM
8-dimethylamino-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 0.0018 mM
8-methyl-2-(4-fluorophenyl)-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
-
8-methylamino-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 0.0018 mM
8-nitro-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 0.004 mM
acetamide,N-[2-[[2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-yl]amino]ethyl]
-
-
Acetylsalicylate
-
weak inhibition of IKK-2
Acetylsalicylic acid
-
nonspecific for IKK, anti-inflammatory
antirheumatic gold compound
-
inhibition of IKKbeta
-
arsenic trioxide
-
nonspecific for IKK, acts on a cystein ersidue in the activation loop
arsenite
-
inhibition of IKKbeta
AS602868
-
IKKbeta inhibitor
-
AS602868
-
inhibitor of IKK-beta
-
AS602868
-
-
-
Berberine
-
an isoquinoline alkaloid derived from a plant used traditionally in Chinese and Ayurvedic medicine inhibits IKK activity. Addition of DTT to the kinase reaction reverses the berberine-mediated inhibition of IKK activity
BI605906
-
an IKKbeta inhibitor
-
BMS-345541
-
specific for IKK-2, binds at an allosteric site
BMS345541
-
shows efficacy in a mouse model of collagen-induced arthritis without signs of major toxicology
BX795
-
-
-
COMPOUND A
-
leads to a significant reduction of Panc-1 cell and MiaPaCa-2 cell growth
curcumin
-
weak inhibition of IKK-2
cyclopentenone prostaglandins
-
nonspecific for IKK, anti-inflammatory
cyclopentenone prostaglandins
-
inhibition of IKKbeta
cyclopentenone prostanoids
-
inhibition of IKK and thus inhibition of NFkappaB-mediated HSV-1-induced HIV-1 replication
cyclopentone prostaglandines
-
inhibition of IKK-2
ethanol,N-[2-[[2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-yl]amino]ethyl]
-
-
evodiamine
-
alkaloid extracted from Evodia rutaecarpa fruits exhibiting antiproliferative, antimetastatic, and apoptotic activities, inhibits IKKalpha activity, suppresses IKKalpha phosphorylation and degradation, and specifically blocks NF-kappaB activation by IKK and other agents, translocation, and activity, overview
IMD-0354
-
in macrophages, the inhibition of IkappaB kinase beta (IKKbeta) results in lower proinflammatory cytokine expression caused by heat-killed Helicobacter pylori cells. Treatment with IKKbeta inhibitor results in milder inflammation in gerbils with Helicobacter pylori gastritis
IMD-0354
-
specific IKKbeta inhibition
LY294002
-
phosphorylation of IKKalphaT23 is inhibited both by LY294002 and wortmannin, but phosphorylation of Ser176/Ser180 is not
methyl (6-chloro-9H-beta-carbolin-8-yl)carbamate
-
inhibits IKK with IC50 of 700 nM
MRT67307
-
an IKKepsilon/TBK1 kinase inhibitor
-
MX781
-
0.02 mM inhibit IKKbeta by 65% in the presence of an ATP concentration corresponding to its Km value
N,1-dimethyl-7-phenyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
;
N,1-dimethyl-7-phenyl-1H-pyrazolo[5,1-b]purin-4-amine
-
-
N,3,8-trimethyl-2-phenyl-3,8-dihydrodiimidazo[4,5-b:4',5'-d]pyridin-5-amine
-
;
N,8-dimethyl-2-phenyl-8H-imidazo[4,5-d][1,3]oxazolo[5,4-b]pyridin-5-amine
-
;
N,8-dimethyl-2-phenyl-8H-imidazo[4,5-d][1,3]thiazolo[5,4-b]pyridin-5-amine
-
;
N,N-dimethyl-3-[(4-[[(6-phenylisoquinolin-7-yl)oxy]methyl]piperidin-1-yl)sulfonyl]propan-1-amine
-
-
N-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine
-
-
N-(2-aminoethyl)-4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzamide
-
IC50 for the IKK complex is 0.0044 mM
N-(2-dimethyl-aminoethyl)-4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzamide
-
IC50 for the IKK complex is 300 nM, cellular profile
N-(2-pyrrolidin-1-yl-ethyl)-4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzamide
-
IC50 for the IKK complex is 500 nM
N-(3,5-bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide
-
-
-
N-(3-methyl-butyl)-4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzamide
-
IC50 for the IKKbeta is above 0.1 mM
N-(6-chloro-9H-beta-carbolin-8-yl)-2-(pyridin-2-yl)acetamide
-
inhibits IKK with IC50 of 0.003 mM
N-(6-chloro-9H-beta-carbolin-8-yl)-2-methoxybenzamide
-
inhibits IKK with IC50 of 0.02 mM
N-(6-chloro-9H-beta-carbolin-8-yl)-3-methoxybenzamide
-
inhibits IKK with IC50 of 600 nM
N-(6-chloro-9H-beta-carbolin-8-yl)-4-hydroxybutanamide
-
inhibits IKK with IC50 of 0.02 mM
N-(6-chloro-9H-beta-carbolin-8-yl)-4-methoxybenzamide
-
inhibits IKK with IC50 of 0.0013 mM
N-(6-chloro-9H-beta-carbolin-8-yl)acetamide
-
inhibits IKK with IC50 of 600 nM
N-(6-chloro-9H-beta-carbolin-8-yl)benzamide
-
inhibits IKK with IC50 of 700 nM
N-(6-chloro-9H-beta-carbolin-8-yl)benzenesulfonamide
-
inhibits IKK with IC50 of 0.02 mM
N-(6-chloro-9H-beta-carbolin-8-yl)methanesulfonamide
-
inhibits IKK with IC50 of 0.0083 mM
N-(6-chloro-9H-beta-carbolin-8-yl)morpholine-4-carboxamide
-
inhibits IKK with IC50 of 0.02 mM
N-(6-chloro-9H-beta-carbolin-8-yl)pyridine-2-carboxamide
-
inhibits IKK with IC50 of 0.001 mM
N-(6-chloro-9H-beta-carbolin-8-yl)pyridine-4-carboxamide
-
inhibits IKK with IC50 of 300 nM
N-(8-methyl-2-phenylimidazo[1,2-a]thieno[3,2-e]pyrazin-5-yl)ethane-1,2-diamine
-
-
N-acetylcysteine
-
inhibits phosphorylation of IkappaBalpha
N-benzyl-6-chloro-9H-beta-carbolin-8-amine
-
inhibits IKK with IC50 of 0.02 mM
N-ethyl-2-(4-fluorophenyl)-N-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
-
N-methyl-2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
-
N-tosyl-L-phenylalanine chloromethyl ketone
-
-
N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]-1,2,3-thiadiazole-4-carboxamide
-
;
N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]acetamide
-
;
N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]butanediamide
-
-
N-[5-[4-(cyclopropylamino)-1-methyl-1H-pyrazolo[5,1-b]purin-7-yl]-2-fluorobenzyl]acetamide
-
-
N-[[2-fluoro-5-[8-methyl-5-methylamino-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]acetamide
-
-
N-[[2-fluoro-5-[8-methyl-5-methylamino-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]methanesulfonamide
-
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]-1,2,3-thiadiazole-5-amide
-
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]acetamide
-
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]isoxazole-5-amide
-
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]methanesulfonamide
-
-
N1-(1,8-dimethylimidazo-[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine
-
i.e. PHA-068E
N2,N2-dimethyl-N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]glycinamide
-
-
NBD peptide
-
NEMO-binding domain peptide
-
nimbolide
-
nimbolide inhibits TNF-alpha-induced p65 nuclear translocation and phosphorylation. Nimbolide binds to and inhibits IKK activation. It suppresses NF-betaB activation by inhibition of IkappaBbeta kinase, wild-type not IKKbeta mutant C179A, leading to suppression of IkappaBalpha phosphorylation and degradation, nuclear translocation, DNA binding, and gene transcription
noraristeromycin
-
NAM
PHA-408
-
selective IKK-2 inhibitor
PHA-408
-
a selective IKK-2 inhibitor, shows time-dependent binding to the enzyme
prostaglandin 2alpha
-
inhibits IKK
Prostaglandin A1
-
strongly inhibits IKK
Prostaglandin A2
-
strongly inhibits IKK
prostaglandin E1
-
inhibits IKK
prostaglandin E2
-
inhibits IKK
protein HSCARG
-
or NMRAL1, NmrA-like family domain-containing protein 1, inhibits the phosphorylation of IKKbeta
-
PS-1145
-
i.e. 8-(NHC(O)-3'-pyridyl)-6-chloro-beta-carboline, inhibits IKK with IC50 of 100 nM in vitro, blocks phosphorylation of IkappaBalpha and subsequent activation of NFkappaB in vivo
PS1145
-
inhibits IKK, blocks TNFalpha activation by IKK in vivo
Rapamycin
-
suppresses IKK activity potentailly through dissociation of raptor from the mTOR complex; suppresses IKK activity potentailly through dissociation of raptor from the mTOR complex
RNAi
-
specific IKKbeta inhibition
-
S1627
-
specific for the IKK complex, inhibits purified IKK in vitro with IC50 of 0.02 mM, inhibits IKK and NFkappaB nuclear translocation in vivo in umbilical vein endothelial cells and in rats, overview
-
S1627
-
preferentially inhibits the beta-subunit of the IKK complex. Specific inhibition of I-kappaB kinase by S1627 modulates the nociceptive response in various nociceptive models in rats. S1627 inhibits the activation of NF-kappaB in the spinal cord and thereby thermal and mechanical hyperalgesia in the zymosan-induced paw inflammation model and the inflammatory edema. It also reduces tactile and cold allodynia in a model of neuropathic pain
-
salicylate
-
weak inhibition of IKK-2
shRNA
-
-
-
sulfasalazine
-
weak inhibition of IKK-2
sulfasalazine
-
nonspecific for IKK, anti-inflammatory
sulindac sulfide
-
nonspecific for IKK, anti-inflammatory
tetrandrine
-
a bis-benzylisoquinoline alkaloid isolated from the roots of Han-Fang-Ji (Stephania Tetrandra S Moore) effectively inhibits IKKs phosphorylation
trans-resveratrol
-
nonspecific for IKK, anti-inflammatory
vaccina virus virulence factor B14
-
interacts and inhibits IKKcomplex. Interaction between vaccina virus virulence factor B14 and IKK complex requires IKKbeta but not IKKalpha
-
vaccinia virus virulence factor B14
-
interacts and inhibits IKKcomplex. Interaction between B14 and IKK complex requires IKKbeta but not IKKalpha
-
Wortmannin
-
phosphorylation of IKKalphaT23 is inhibited both by LY294002 and wortmannin, but phosphorylation of Ser176/Ser180 is not
YopJ
-
effector protein YopJ from Yersinia pestis inhibits MAPK kinase and IKK activation by acetylating the conserved serine and threonine residues in the activation loop of the kinase. Furthermore, YopJ inhibits Tax-mediated IkappaB phosphorylation
-
methyl 1-(3-amino-2-carbamoyl-4-propylthieno[2,3-b]pyridin-6-yl)piperidine-4-carboxylate
-
-
additional information
-
CREB-binding protein-bound NEMO/IKKgamma inhibits IKKalpha and p65 transcriptional activities
-
additional information
-
evodiamine analogue rutaecarpine does not inhibit IKK and NF-kappaB activation
-
additional information
-
simvastatin inhibits the TNFalpha-induced activation of IkappaB kinase and activation of NF-kappaB in vitro and in vivo, simvastatin highly affects the whole NF-kappaB-dependent pathway of signaling, overview
-
additional information
-
prolyl hydroxylase-1 negatively regulates IKKbeta, hydroxylation represses IKKbeta activity by altering protein expression or by preventing its activation through phosphorylation on S177/S181
-
additional information
-
two structurally unrelated kinase inhibitors, termed NG25 or 5Z-7-oxozeaenol, inhibit the TAK1 protein kinase, and therefore also inhibit activation of IKKalpha and IKKbeta
-
additional information
-
structure-based design of IKK-2 inhibitors based on induced-fit docking into the homology model, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
alloferon
-
alloferon, a 13-amino acid peptide isolated from the bacteria-challenged larvae of the blow fly Calliphora vicina, activates IKK activity
CD28
-
activates Vav-1/IKKalpha and subsequently NFkappaB, meditated by Vav-1
-
cdc37
-
the chaperone protein associates with the IKK complex and is required for its TNFalpha-induced activation
-
glycogen synthase kinase-3beta
-
GSK-3 is required for constitutive IKK activity; GSK-3 is required for constitutive IKK activity
-
HSP70
-
the chaperone protein associates with the IKK complex and is required for its TNFalpha-induced activation
-
Hsp90
-
the chaperone protein associates with the IKK complex and is required for its TNFalpha-induced activation
-
mTOR
-
mTOR (mammalian target of rapamycin) controls phosphorylation of IkappaBalpha and p65/RelA as shown by knockdown of mTOR in PC3 cells. Furthermore, overexpression of mTOR stimulates IKK activity; mTOR (mammalian target of rapamycin) controls phosphorylation of IkappaBalpha and p65/RelA as shown by knockdown of mTOR in PC3 cells. Furthermore, overexpression of mTOR stimulates IKK activity
-
NEMO
-
-
-
NEMO
-
i.e. NF-kappaB essential modifier, complexing with IkappaB kinase-gamma and ubiquination, involving the zinc finger of NEMO and c-IAP1, are required for activation of the IkappaB kinase complex by inflammatory stimuli such as tumor necrosis factor TNFalpha
-
NEMO
-
i.e. NF-kappaB essential modifier, complexing with IkappaB kinase-gamma, regulates cytokine-induced IKK complex activity, NEMO/IKKgamma is shuttling between cytoplasm and nucleus, and binds CBP, being ininvolved in NFkappaB regulation
-
NEMO
-
i.e. NF-kappaB essential modifier, complexing with IkappaB kinase-gamma
-
NEMO
-
i.e. NF-kappaB essential modifier, complexing with IkappaB kinase-gamma and ubiquitination, involving the zinc finger of NEMO and c-IAP1, are required for activation of the IkappaB kinase complex by inflammatory stimuli such as tumor necrosis factor TNFalpha
-
raptor
-
raptor (mTOR associated protein) controls phosphorylation of IkappaBalpha and p65/RelA as shown by knockdown of raptor in PC3 cells; raptor (mTOR associated protein) controls phosphorylation of IkappaBalpha and p65/RelA as shown by knockdown of raptor in PC3 cells
-
TAK1
-
critical direct upsteam activating kinase of IKK
-
Tax
-
viral oncoprotein, activates by direct binding, involved in ubiquitination and phosphorylation
-
TNF-alpha
-
-
-
TNFalpha
-
and other cytokines, activation of IKK activating NF-kappaB
-
TNFalpha
-
activates histone H3 phosphorylation activity, TNFalpha-induced activation of IKK-beta but not IKK-alpha leads to rapid NFkappaB activation and subsequent degradation of IkappaB
-
TNFalpha
-
induces IKK activity, activation is negatively feedback regulated
-
TRAF6
-
upstream activator of IKK kinase complex
-
tumor necrosis factor TNFalpha
-
cytokines activate the IKK complex, mechanism, overview
-
Vav-1
-
cytoplasmic proto-oncogene, constitutively associates with IKKalpha in Jurkat and primary CD4+ cells
-
human leukemia virus type-1 TAX
-
TAX is binding to and activating the IKK complex. A sustained activation of the Tax-mediated activation of the NFkappaB pathway is dependent on an intact Hsp90-IKK complex
-
additional information
-
herpesvirus HSV-1 potently induces IkappaB kinase IKK causing persistent induction of NFkappaB resulting in transactivation of HIV-1-LTR-regulated genes and induction of HIV-1 replication in infected T-cells
-
additional information
-
IKKgamma phosphorylation by IKKbeta is induced by the cytokine TNFalpha and the viral oncoprotein Tax
-
additional information
-
TNFalpha, TGF-beta-activated kinase 1 TAK1, IKKalpha subunit and IKKbeta subunit induce IKK phosphorylation activity, overview
-
additional information
-
IKK is induced by TNFalpha
-
additional information
-
IKK induction by cytokines, transcriptional activation by CREB-binding protein, i.e. CBP, after N-terminally binding to NEMO, which competes with IKKalpha and p65
-
additional information
-
aldosterone regulates IKKbeta activity by enzyme induction
-
additional information
-
IKKgamma phosphorylation by IKKbeta is induced by the cytokine TNF-R1, IKKbeta is recruited to the cytoplasmic tail of TNF-R1 by adaptor proteins, such as RIP
-
additional information
-
lipopolysaccharides from Escherichia coli induce enzyme activity versus RelA/p65 and NFkappaB activation in vivo, induction is not inhibited by LY294002, overview
-
additional information
-
infection and genome insertion of human cytomegalovirus induces expression of the catalytic subunit IKK2 in the host cell which is required for viral induction of NF-kappaB activation and involved in viral replication and lytic cycle
-
additional information
-
type 1 TNFalpha induces the enzyme activity
-
additional information
-
cytokine-induced activation of IKK, e.g. by TNFalpha, required for NFkappaB activation, leads to rapid degradation of IkappaB
-
additional information
-
TNF-alpha induced association of IKK-alpha with p65 and CBP
-
additional information
-
lipopolysaccharides stimulate cytokine-mediated IKK activity being positively feedback regulated
-
additional information
-
the IkappaB complex gets activated by phosphorylation, the enzyme activity is induced by proinflammatory cytokines and by oxidative and genotoxic stress, mechanisms/pathways of activation and derepression of the IKK complex, overview
-
additional information
-
IKKbeta is activated by phosphorylation at Ser171 and Ser181 of the activation loop
-
additional information
-
no activation by arsenic nor H2O2
-
additional information
-
TNFalpha induces activation of IkappaB kinase, which is inhibited by simvastatin
-
additional information
-
hypoxia activates NFkappaB through a pathway involving activation of IkappaB kinase-beta, IKKbeta
-
additional information
-
Bcl10 degradation depends on NEMO and CARMA1
-
additional information
-
virus-inducible expression of IKKepsilon, IKKepsilon is activated by IFNbeta
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
additional information
-
kinetics of IkappaB phosphorylation by parasite IKK, host NF-kappaB activation reveals a biphasic, hierarchical, and temporally regulated response
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000006
-
8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0022
-
(4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)phenyl)acetic acid
-
IC50 for the IKKbeta is 0.0022 mM
0.00052
-
1,4-dimethyl-7-methylamino-2-phenyl-4H-imidazo[4,5-d]imidazo[5,4-b]pyridine
-
IKK-2
0.0043
-
1,4-dimethyl-7-methylamino-2-phenyl-4H-imidazo[4,5-d]imidazo[5,4-b]pyridine
-
IKK-1
0.02
-
1-(6-chloro-9H-beta-carbolin-8-yl)-3-methylurea
-
inhibits IKK with IC50 of 0.02 mM
0.0008
-
1-[3-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanamine
-
IKK-beta
0.0126
-
1-[3-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanamine
-
IKK-alpha
0.0001
-
1-[4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanamine
-
IKK-beta
0.0063
-
1-[4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanamine
-
IKK-alpha
0.0004
-
1-[4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanesulfonamide
-
IKK-beta
0.004
-
1-[4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]phenyl]methanesulfonamide
-
IKK-alpha
0.0003
-
17-acetoxyjolkinolide B
-
-
0.000056
-
2-(4-fluorophenyl)-8-methyl-N-[2-(piperidin-1-yl)ethyl]-8H-imidazo[4,5-d][1,3]thiazolo[5,4-b]pyridin-5-amine
-
IKK-2
0.0083
-
2-(4-fluorophenyl)-8-methyl-N-[2-(piperidin-1-yl)ethyl]-8H-imidazo[4,5-d][1,3]thiazolo[5,4-b]pyridin-5-amine
-
IKK-1
0.1
-
2-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzoic acid
-
IC50 for the IKK complex is above 0.1 mM
0.000025
-
2-hydroxy-N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]acetamide
-
-
0.000081
-
2-methanesulfonyl-4-methyl-7-methylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.0076
-
2-methanesulfonyl-4-methyl-7-methylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.000009
-
2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7yl)pyridin-2-yl)methyl)acetamide
-
IKKbeta catalyzed phosphorylation of IkappaBalpha
0.00029
-
2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7yl)pyridin-2-yl)methyl)acetamide
-
IkappaBalpha phosphorylation in peripheral blood mononuclear cell
0.00496
-
2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7yl)pyridin-2-yl)methyl)acetamide
-
IKKalpha catalyzed phosphorylation of IkappaBalpha
0.001
-
3-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzoic acid
-
IC50 for the IKKbeta is 0.001 mM
0.0027
-
3-amino-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0169
-
3-amino-4-(1-benzofuran-2-yl)-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0108
-
3-amino-4-(2-methoxyethoxy)thieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.014
-
3-amino-4-(4-chlorophenyl)-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.02
-
3-amino-4-(4-hydroxyphenyl)-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta, larger than 0.0200
0.002
-
3-amino-4-ethoxythieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0011
-
3-amino-4-furan-2-yl-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0047
-
3-amino-4-methoxythieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0025
-
3-amino-4-methyl-6-morpholin-4-ylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00068
-
3-amino-4-methyl-6-piperazin-1-ylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0024
-
3-amino-4-methyl-6-piperidin-1-ylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0022
-
3-amino-4-propoxythieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.000072
-
3-amino-6-(1,4-diazepan-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0029
-
3-amino-6-(2-aminoethoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0066
-
3-amino-6-(2-hydroxyethoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00063
-
3-amino-6-(3-aminoazepan-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.05
-
3-amino-6-(3-aminopropoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta, larger than 0.0500
0.0024
-
3-amino-6-(3-hydroxypiperidin-1-yl)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00057
-
3-amino-6-(3-hydroxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.013
-
3-amino-6-(3-hydroxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
whole blood assay
0.0133
-
3-amino-6-(3-hydroxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKalpha
0.0051
-
3-amino-6-(3-hydroxypropoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00014
-
3-amino-6-(3-oxo-1,4-diazepan-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.002
-
3-amino-6-(3-oxopiperazin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.000041
-
3-amino-6-(4-aminopiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00009
-
3-amino-6-(4-aminopiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKalpha
0.0016
-
3-amino-6-(4-aminopiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
whole blood assay
0.00015
-
3-amino-6-(4-carbamoylpiperazin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0013
-
3-amino-6-(4-carbamoylpiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00075
-
3-amino-6-(4-hydroxypiperidin-1-yl)-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00028
-
3-amino-6-(4-hydroxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0098
-
3-amino-6-(4-hydroxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
whole blood assay
0.0112
-
3-amino-6-(4-hydroxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKalpha
0.00068
-
3-amino-6-(4-methoxypiperidin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00052
-
3-amino-6-(4-methylpiperazin-1-yl)-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0025
-
3-amino-6-methyl-4-(2-methylpropyl)thieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0085
-
3-amino-6-methyl-4-(4-methylphenyl)thieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0074
-
3-amino-6-methyl-4-phenylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0013
-
3-amino-6-methyl-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.006
-
3-amino-6-methyl-4-pyridin-2-ylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.002
-
3-amino-6-methyl-4-thiophen-2-ylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0013
-
3-amino-6-methyl-4-[4-(methylsulfonyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0127
-
3-amino-6-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00012
-
3-amino-6-piperazin-1-yl-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0032
-
3-amino-6-piperazin-1-yl-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
whole blood assay
0.0034
-
3-amino-6-piperazin-1-yl-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKalpha
0.0058
-
3-amino-6-[(2-hydroxyethyl)amino]-4-methylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.0005
-
3-amino-6-[(3R)-3-aminopyrrolidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00195
-
3-amino-6-[(3R)-3-hydroxypyrrolidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00059
-
3-amino-6-[(3S)-3-aminopyrrolidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00145
-
3-amino-6-[(3S)-3-hydroxypyrrolidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00068
-
3-amino-6-[4-(dimethylamino)piperidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.00012
-
3-amino-6-[4-(methylamino)piperidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.000098
-
3-amino-6-[4-[(methylsulfonyl)amino]piperidin-1-yl]-4-propylthieno[2,3-b]pyridine-2-carboxamide
-
IKKbeta
0.000012
-
3-methoxy-N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]propanamide
-
-
0.00262
-
3-methoxy-N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]propanamide
-
-
0.000007
-
3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzonitrile
-
-
0.0079
-
3-[7-(benzyloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-beta
0.0251
-
3-[7-(benzyloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-alpha, less than 0.0251
0.0013
-
3-[7-(piperidin-4-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-beta
0.0079
-
3-[7-(piperidin-4-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-alpha
0.00025
-
4-(1-benzothiophen-2-yl)-N-[3-chloro-4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 250 nM
0.00015
-
4-(1-benzothiophen-2-yl)-N-[3-methoxy-4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 150 nM
0.0085
-
4-(1-benzothiophen-2-yl)-N-[4-(pyrrolidin-1-ylcarbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 0.0085 mM, cellular profile
0.00008
-
4-(1-benzothiophen-2-yl)-N-[4-([4-(dimethyl-amino)piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 80 nM, cellular profile
0.00007
-
4-(1-benzothiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 70 nM, cellular profile
0.0008
-
4-(5-(3-acetamino-3-methylbutyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 800 nM
0.00003
-
4-(5-(3-amino-3-ethylpentyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 30 nM
0.0002
-
4-(5-(3-amino-3-methyl-but-1-ynyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 200 nM
0.00004
-
4-(5-(3-amino-3-methyl-butyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 40 nM
0.00005
-
4-(5-(3-hydroxy-3-methylbutyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amin
-
IC50 for the IKK complex is 50 nM, cellular profile
0.0001
-
4-(5-(3-methoxypropyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 100 nM, cellular profile
0.00004
-
4-(5-(4-hydroxybutyl)thiophen-2-yl)-N-[4-([4-pyrrolidin-1-yl-piperidin-1-yl]carbonyl)phenyl]pyrimidin-2-amine
-
IC50 for the IKK complex is 40 nM, cellular profile
0.001
-
4-(7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]isoquinolin-6-yl)benzenesulfonamide
-
IKK-beta
0.0251
-
4-(7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]isoquinolin-6-yl)benzenesulfonamide
-
-
0.018
-
4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzoic acid
-
IC50 for the IKK complex is 0.018 mM, cellular profile
0.00013
-
4-methyl-7-methylamino-2-(azepan-1-yl)-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.000028
-
4-methyl-7-methylamino-2-(methylthio)-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.0026
-
4-methyl-7-methylamino-2-(methylthio)-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.0015
-
4-methyl-7-methylamino-2-benzylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.00016
-
4-methyl-7-methylamino-2-cyclopentylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.0025
-
4-methyl-7-methylamino-2-diethylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.02
-
4-methyl-7-methylamino-2-diethylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.000015
-
4-methyl-7-methylamino-2-ethylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.0011
-
4-methyl-7-methylamino-2-ethylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.0003
-
4-methyl-7-methylamino-2-hydroxyethylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.000015
-
4-methyl-7-methylamino-2-methylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.00084
-
4-methyl-7-methylamino-2-methylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.00092
-
4-methyl-7-methylamino-2-methylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.0034
-
4-methyl-7-methylamino-2-methylamino-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.000011
-
4-methyl-7-methylamino-2-phenyl-4H-imidazo[4,5-d]oxazolo[5,4-b]pyridine
-
IKK-2
0.00027
-
4-methyl-7-methylamino-2-phenyl-4H-imidazo[4,5-d]oxazolo[5,4-b]pyridine
-
IKK-1
0.000006
-
4-methyl-7-methylamino-2-phenyl-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.0035
-
4-methyl-7-methylamino-2-phenyl-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.00021
-
4-methyl-7-methylamino-2-piperidine-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.0061
-
4-methyl-7-methylamino-2-piperidine-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.000015
-
4-methyl-7-methylamino-2-thienylamido-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.000033
-
4-methyl-7-methylamino-2-[1,2,3,6-tetrahydropyridine]-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-2
0.0081
-
4-methyl-7-methylamino-2-[1,2,3,6-tetrahydropyridine]-4H-imidazo[4,5-d]thiazolo[5,4-b]pyridine
-
IKK-1
0.0032
-
4-[7-(benzyloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-beta
0.0251
-
4-[7-(benzyloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-alpha, less than 0.0251
0.0008
-
4-[7-(piperidin-3-ylmethoxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-beta
0.005
-
4-[7-(piperidin-3-ylmethoxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-alpha
0.0008
-
4-[7-(piperidin-3-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-beta
0.0126
-
4-[7-(piperidin-3-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-alpha
0.0006
-
4-[7-(piperidin-4-ylmethoxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-beta
0.0016
-
4-[7-(piperidin-4-ylmethoxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-alpha
0.0001
-
4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-beta
0.0079
-
4-[7-(piperidin-4-yloxy)isoquinolin-6-yl]benzenesulfonamide
-
IKK-alpha
0.0013
-
4-[7-[(1-acetylpiperidin-4-yl)oxy]isoquinolin-6-yl]benzenesulfonamide
-
IKK-beta
0.0251
-
4-[7-[(1-acetylpiperidin-4-yl)oxy]isoquinolin-6-yl]benzenesulfonamide
-
IKK-alpha, less than 0.0251
0.0006
-
5,6-dibromo-beta-carboline
-
inhibits IKK with IC50 of 600 nM
0.0006
-
5-bromo-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 600 nM
0.0011
-
5-bromo-6-cyano-beta-carboline
-
inhibits IKK with IC50 of 0.0011 mM
0.002
-
5-bromo-6-fluoro-beta-carboline
-
inhibits IKK with IC50 of 0.002 mM
0.004
-
5-bromo-6-methoxy-beta-carboline
-
nonspecific inhibitor of IKK, inhibits IKK with IC50 of 0.004 mM
0.0011
-
5-bromo-6-trifluoromethyl-beta-carboline
-
inhibits IKK with IC50 of 0.0011 mM
0.015
-
5-bromo-beta-carboline
-
inhibits IKK with IC50 of 0.015 mM
0.003
-
6,8-dichloro-7-(cyclohexylmethoxy)-9H-beta-carboline
-
inhibits IKK with IC50 of 0.003 mM
0.00014
-
6,8-dichloro-7-ethoxy-9H-beta-carboline
-
inhibits IKK with IC50 of 140 nM
0.00017
-
6,8-dichloro-7-methoxy-9H-beta-carboline
-
inhibits IKK with IC50 of 170 nM
0.0032
-
6,8-dichloro-9H-beta-carbolin-7-yl morpholine-4-carboxylate
-
inhibits IKK with IC50 of 0.0032 mM
0.0002
-
6,8-dichloro-beta-carboline
-
inhibits IKK with IC50 of 200 nM
-
0.0004
-
6-bromo-7-(piperidin-4-yloxy)isoquinoline
-
IKK-beta
0.01
-
6-bromo-7-(piperidin-4-yloxy)isoquinoline
-
IKK-alpha
0.005
-
6-bromo-7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]isoquinoline
-
IKK-beta
0.0251
-
6-bromo-7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]isoquinoline
-
IKK-alpha, less than 0.0251
0.0002
-
6-phenyl-7-(piperidin-3-ylmethoxy)isoquinoline
-
IKK-beta
0.0032
-
6-phenyl-7-(piperidin-3-ylmethoxy)isoquinoline
-
IKK-alpha
0.0006
-
6-phenyl-7-(piperidin-3-yloxy)isoquinoline
-
IKK-beta
0.004
-
6-phenyl-7-(piperidin-3-yloxy)isoquinoline
-
IKK-alpha
0.0013
-
6-phenyl-7-(piperidin-4-ylmethoxy)isoquinoline
-
IKK-beta
0.01
-
6-phenyl-7-(piperidin-4-ylmethoxy)isoquinoline
-
IKK-alpha
0.0001
-
6-phenyl-7-(piperidin-4-yloxy)isoquinoline
-
IKK-beta
0.0025
-
6-phenyl-7-(piperidin-4-yloxy)isoquinoline
-
IKK-alpha
0.004
-
6-phenyl-7-(pyridin-3-ylmethoxy)isoquinoline
-
IKK-beta
0.0251
-
6-phenyl-7-(pyridin-3-ylmethoxy)isoquinoline
-
IKK-alpha, less than 0.0251
0.005
-
6-phenyl-7-(pyridin-4-ylmethoxy)isoquinoline
-
IKK-beta
0.0251
-
6-phenyl-7-(pyridin-4-ylmethoxy)isoquinoline
-
IKK-alpha, less than 0.0251
0.000044
-
7-(2-fluorophenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
0.000007
-
7-(3-fluorophenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
0.000008
-
7-(3-methoxyphenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
0.000043
-
7-(4-fluorophenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
0.00173
-
7-(4-fluorophenyl)-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
0.00008
-
7-(OCH2CH(CH2CH2))-6,8-dichloro-beta-carboline
-
inhibits IKK with IC50 of 80 nM
-
0.005
-
7-(piperidin-4-yloxy)isoquinoline
-
IKK-beta
0.0251
-
7-(piperidin-4-yloxy)isoquinoline
-
IKK-alpha, less than 0.0251
0.011
-
7-hydroxy-6,8-dichloro-beta-carboline
-
inhibits IKK with IC50 of 0.011 mM
-
0.0126
-
7-[(1-acetylpiperidin-4-yl)oxy]-6-bromoisoquinoline
-
IKK-beta
0.0251
-
7-[(1-acetylpiperidin-4-yl)oxy]-6-bromoisoquinoline
-
IKK-alpha, less than 0.0251
0.0016
-
7-[(1-acetylpiperidin-4-yl)oxy]-6-phenylisoquinoline
-
IKK-alpha
0.0032
-
7-[(1-acetylpiperidin-4-yl)oxy]-6-phenylisoquinoline
-
IKK-beta
0.000011
-
7-[3-(aminomethyl)phenyl]-N,1-dimethyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
0.0025
-
7-[[1-(ethylsulfonyl)piperidin-4-yl]methoxy]-6-phenylisoquinoline
-
IKK-beta
0.02
-
7-[[1-(ethylsulfonyl)piperidin-4-yl]methoxy]-6-phenylisoquinoline
-
IKK-alpha
0.002
-
7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]-6-phenylisoquinoline
-
IKK-beta
0.0126
-
7-[[1-(ethylsulfonyl)piperidin-4-yl]oxy]-6-phenylisoquinoline
-
IKK-alpha
0.00004
-
8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
-
-
0.0141
-
8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
-
-
0.0013
-
8-amino-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 0.0013 mM
0.0018
-
8-dimethylamino-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 0.0018 mM
0.00018
-
8-methyl-2-(4-fluorophenyl)-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
IKK-2
0.02
-
8-methyl-2-(4-fluorophenyl)-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
IKK-1, larger than 0.020
0.0018
-
8-methylamino-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 0.0018 mM
0.004
-
8-nitro-6-chloro-beta-carboline
-
inhibits IKK with IC50 of 0.004 mM
0.000033
-
acetamide,N-[2-[[2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-yl]amino]ethyl]
-
IKK-2
0.005
-
acetamide,N-[2-[[2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-yl]amino]ethyl]
-
IKK-1
0.000041
-
BX795
-
-
-
0.007
-
chalcone
-
-
0.000075
-
ethanol,N-[2-[[2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-yl]amino]ethyl]
-
IKK-2
0.0086
-
ethanol,N-[2-[[2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-yl]amino]ethyl]
-
IKK-1
0.0007
-
methyl (6-chloro-9H-beta-carbolin-8-yl)carbamate
-
inhibits IKK with IC50 of 700 nM
0.0078
-
methyl 1-(3-amino-2-carbamoyl-4-propylthieno[2,3-b]pyridin-6-yl)piperidine-4-carboxylate
-
IKKbeta
0.00004
-
N,1-dimethyl-7-phenyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
0.00167
-
N,1-dimethyl-7-phenyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine
-
-
0.000034
-
N,1-dimethyl-7-phenyl-1H-pyrazolo[5,1-b]purin-4-amine
-
IKK-2
0.00099
-
N,1-dimethyl-7-phenyl-1H-pyrazolo[5,1-b]purin-4-amine
-
IKK-1
0.00052
-
N,3,8-trimethyl-2-phenyl-3,8-dihydrodiimidazo[4,5-b:4',5'-d]pyridin-5-amine
-
-
0.00428
-
N,3,8-trimethyl-2-phenyl-3,8-dihydrodiimidazo[4,5-b:4',5'-d]pyridin-5-amine
-
-
0.000011
-
N,8-dimethyl-2-phenyl-8H-imidazo[4,5-d][1,3]oxazolo[5,4-b]pyridin-5-amine
-
-
0.00027
-
N,8-dimethyl-2-phenyl-8H-imidazo[4,5-d][1,3]oxazolo[5,4-b]pyridin-5-amine
-
-
0.000006
-
N,8-dimethyl-2-phenyl-8H-imidazo[4,5-d][1,3]thiazolo[5,4-b]pyridin-5-amine
-
-
0.0035
-
N,8-dimethyl-2-phenyl-8H-imidazo[4,5-d][1,3]thiazolo[5,4-b]pyridin-5-amine
-
-
0.0013
-
N,N-dimethyl-3-[(4-[[(6-phenylisoquinolin-7-yl)oxy]methyl]piperidin-1-yl)sulfonyl]propan-1-amine
-
IKK-beta
0.01
-
N,N-dimethyl-3-[(4-[[(6-phenylisoquinolin-7-yl)oxy]methyl]piperidin-1-yl)sulfonyl]propan-1-amine
-
IKK-alpha
0.0003
-
N-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine
-
IKK-2
0.004
-
N-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine
-
IKK-1
0.0044
-
N-(2-aminoethyl)-4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzamide
-
IC50 for the IKK complex is 0.0044 mM
0.0003
-
N-(2-dimethyl-aminoethyl)-4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzamide
-
IC50 300 nM for the IK cellular profile
0.0005
-
N-(2-pyrrolidin-1-yl-ethyl)-4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzamide
-
IC50 for the IKK complex is 500 nM
0.1
-
N-(3-methyl-butyl)-4-([4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino)benzamide
-
IC50 for the IKKbeta is above 0.1 mM
0.003
-
N-(6-chloro-9H-beta-carbolin-8-yl)-2-(pyridin-2-yl)acetamide
-
inhibits IKK with IC50 of 0.003 mM
0.02
-
N-(6-chloro-9H-beta-carbolin-8-yl)-2-methoxybenzamide
-
inhibits IKK with IC50 of 0.02 mM
0.0006
-
N-(6-chloro-9H-beta-carbolin-8-yl)-3-methoxybenzamide
-
inhibits IKK with IC50 of 600 nM
0.02
-
N-(6-chloro-9H-beta-carbolin-8-yl)-4-hydroxybutanamide
-
inhibits IKK with IC50 of 0.02 mM
0.0013
-
N-(6-chloro-9H-beta-carbolin-8-yl)-4-methoxybenzamide
-
inhibits IKK with IC50 of 0.0013 mM
0.0006
-
N-(6-chloro-9H-beta-carbolin-8-yl)acetamide
-
inhibits IKK with IC50 of 600 nM
0.0007
-
N-(6-chloro-9H-beta-carbolin-8-yl)benzamide
-
inhibits IKK with IC50 of 700 nM
0.02
-
N-(6-chloro-9H-beta-carbolin-8-yl)benzenesulfonamide
-
inhibits IKK with IC50 of 0.02 mM
0.0083
-
N-(6-chloro-9H-beta-carbolin-8-yl)methanesulfonamide
-
inhibits IKK with IC50 of 0.0083 mM
0.02
-
N-(6-chloro-9H-beta-carbolin-8-yl)morpholine-4-carboxamide
-
inhibits IKK with IC50 of 0.02 mM
0.001
-
N-(6-chloro-9H-beta-carbolin-8-yl)pyridine-2-carboxamide
-
inhibits IKK with IC50 of 0.001 mM
0.0003
-
N-(6-chloro-9H-beta-carbolin-8-yl)pyridine-4-carboxamide
-
inhibits IKK with IC50 of 300 nM
0.000019
-
N-(8-methyl-2-phenylimidazo[1,2-a]thieno[3,2-e]pyrazin-5-yl)ethane-1,2-diamine
-
IKK-2
0.0004
-
N-(8-methyl-2-phenylimidazo[1,2-a]thieno[3,2-e]pyrazin-5-yl)ethane-1,2-diamine
-
IKK-1
0.02
-
N-benzyl-6-chloro-9H-beta-carbolin-8-amine
-
inhibits IKK with IC50 of 0.02 mM
0.000039
-
N-ethyl-2-(4-fluorophenyl)-N-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
IKK-2
0.0034
-
N-ethyl-2-(4-fluorophenyl)-N-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
IKK-1
0.000026
-
N-methyl-2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
IKK-2
0.0031
-
N-methyl-2-(4-fluorophenyl)-8-methyl-8H-imidazo[4,5-d]thiazolo[5,4-b]pyridine-5-amine
-
IKK-1
0.000039
-
N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]-1,2,3-thiadiazole-4-carboxamide
-
-
0.00015
-
N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]-1,2,3-thiadiazole-4-carboxamide
-
-
0.000014
-
N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]acetamide
-
-
0.000633
-
N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]acetamide
-
-
0.000022
-
N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]butanediamide
-
-
0.00028
-
N-[5-[4-(cyclopropylamino)-1-methyl-1H-pyrazolo[5,1-b]purin-7-yl]-2-fluorobenzyl]acetamide
-
IKK-2
0.0097
-
N-[5-[4-(cyclopropylamino)-1-methyl-1H-pyrazolo[5,1-b]purin-7-yl]-2-fluorobenzyl]acetamide
-
IKK-1
0.000053
-
N-[[2-fluoro-5-[8-methyl-5-methylamino-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]acetamide
-
IKK-2
0.0035
-
N-[[2-fluoro-5-[8-methyl-5-methylamino-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]acetamide
-
IKK-1
0.000032
-
N-[[2-fluoro-5-[8-methyl-5-methylamino-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]methanesulfonamide
-
IKK-2
0.0042
-
N-[[2-fluoro-5-[8-methyl-5-methylamino-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]methanesulfonamide
-
IKK-1
0.000016
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]-1,2,3-thiadiazole-5-amide
-
IKK-2
0.001
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]-1,2,3-thiadiazole-5-amide
-
IKK-1
0.000022
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]acetamide
-
IKK-2
0.0019
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]acetamide
-
IKK-1
0.000025
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]isoxazole-5-amide
-
IKK-2
0.0014
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]isoxazole-5-amide
-
IKK-1
0.000005
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]methanesulfonamide
-
IKK-2
0.001
-
N-[[3-[8-methyl-5-(methylamino)-8H-imidazo[4,5-d]-thiazolo[5,4-b]pyridine-2-yl]phenyl]methyl]methanesulfonamide
-
IKK-1
0.000079
-
N2,N2-dimethyl-N-[3-[1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]benzyl]glycinamide
-
-
0.00037
-
noraristeromycin
-
IKKalpha
0.00064
-
noraristeromycin
-
inhibited endogenous IKK activity following TNF-alpha stimulation
0.00001
-
PHA-408
-
less than 0.000010
0.0001
-
PS-1145
-
i.e. 8-(NHC(O)-3'-pyridyl)-6-chloro-beta-carboline, inhibits IKK with IC50 of 100 nM in vitro, blocks phosphorylation of IkappaBalpha and subsequent activation of NFkappaB in vivo
0.02
-
S1627
-
specific for the IKK complex, inhibits purified IKK in vitro with IC50 of 0.02 mM, inhibits IKK and NFkappaB nuclear translocation in vivo in umbilical vein endothelial cells and in rats, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
development of real-time imaging for continous enzyme detection and kinetics in intact cells and living mice utilizing a recombinant IkappaBalpha-firefly luciferase reporter construct
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
assay at
7.2
-
-
assay at; assay at
7.2
-
-
assay at
7.2
-
-
activity assay
7.4
-
-
activity assay
7.5
-
-
activity assay
7.5
-
-
assay at
7.6
-
-
assay at
7.6
-
-
activity assay; activity assay
7.6
-
-
aassay at
8
-
-
assay at
8
-
-
assay at
8
-
-
assay at; assay at
8
-
-
assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
activity assay at room temperature
25
-
-
assay at
25
-
-
activity assay; activity assay
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at
30
-
-
assay at; assay at
30
-
-
assay at
30
-
-
activity assay
30
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
additional information
-
-
assay caried out at room temperature
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
-, microRNA hsa-miR-199a regulates IKKbeta expression in epithelial ovarian cancer cells (EOC)
Manually annotated by BRENDA team
-
chronically infected with HIV-1
Manually annotated by BRENDA team
-
peripheral
Manually annotated by BRENDA team
-
bronchial epithelial cell line
Manually annotated by BRENDA team
-
cell line KG-1
Manually annotated by BRENDA team
-
colon cancer cell line
Manually annotated by BRENDA team
-
colon cancer cell line
Manually annotated by BRENDA team
-
partly derived from bone marrow
Manually annotated by BRENDA team
-
from umbilical vein
Manually annotated by BRENDA team
Mus musculus C57BI/6J
-
-
-
Manually annotated by BRENDA team
-
adult and embryonic
Manually annotated by BRENDA team
-
mouse embryonic fibrblasts MEF
Manually annotated by BRENDA team
-
mouse embryonic fibroblasts MEF
Manually annotated by BRENDA team
-
mouse embryonic fibroblasts, MEF
Manually annotated by BRENDA team
-
murine embryonic fibroblast, MEF
Manually annotated by BRENDA team
-
chronically infected with HIV-1
Manually annotated by BRENDA team
-
embryonic kidney cell line
Manually annotated by BRENDA team
-
induced by TNFalpha
Manually annotated by BRENDA team
Mus musculus C57BI/6J
-
-
-
Manually annotated by BRENDA team
-
T-cell lymphoma cell line
Manually annotated by BRENDA team
-
myeloid leukemia cell line
Manually annotated by BRENDA team
-
MCA3D (non-tumorigenic keratinocytes) highest IKK alpha expression, PDVC57 (moderately carcinogenic keratinocytes) show an important reduction in IKK alpha expression, HACa4 cells (highly tumorigenic) expression of IKK alpha is almost absent
Manually annotated by BRENDA team
-
respiratory tract mucosa
Manually annotated by BRENDA team
Mus musculus BALB/c
-
respiratory tract mucosa
-
Manually annotated by BRENDA team
-
alveolar and peritoneal
Manually annotated by BRENDA team
-
activated macrophages are significantly increased in Helicobacter pylori-infected gastric mucosa and are identified as being important cells with potent activation of NF-kappaB, which plays an important part in producing proinflammatory cytokines. Macrophage depletion by the administration of clodronate resulted in milder inflammation in gerbils infected with Helicobacter pylori
Manually annotated by BRENDA team
-
bone marrow-derived or RAW-264.7 macrophages
Manually annotated by BRENDA team
-
lobuloalveolar epithelial cell
Manually annotated by BRENDA team
-
embryonic fibroblast cell line
Manually annotated by BRENDA team
-
embryonic fibroblast cell line, from wild-type and IKKalpha- mice
Manually annotated by BRENDA team
-
wild-type and IKKalpha- or IKKbeta-deficient embryonic fibroblast cell line infected with parasite Toxoplasma gondii, RH strain
Manually annotated by BRENDA team
-
immortal mpkCCDc14 cell line, derived from transgenic mice
Manually annotated by BRENDA team
-
mycosis fungoides cell line
Manually annotated by BRENDA team
-
lung adenocarcinoma cell line
Manually annotated by BRENDA team
-
macrophage cell line
Manually annotated by BRENDA team
-
monocyte/macrophage cell line
Manually annotated by BRENDA team
-
-, microRNA hsa-miR-199a regulates IKKbeta expression in epithelial ovarian cancer cells (EOC)
Manually annotated by BRENDA team
-
in human acantholytic squamous cell carcinoma IKKalpha and E-cadherin are strongly expressed, with absence of keratins K1 and K10, usually co-expressed with IKKalpha and E-cadherin
Manually annotated by BRENDA team
-
cutaneous T-cell lymphoma
Manually annotated by BRENDA team
-
stroma, embryonic
Manually annotated by BRENDA team
-
IKKalpha and IKKbeta expression patterns in different developmental stages during gestation and in different tooth regions, overview
Manually annotated by BRENDA team
-
multiple myeloma cell line
Manually annotated by BRENDA team
additional information
-
a total of 20 primary epithelial ovarian cancer cells are used. The ratio of IKKbeta/IKKalpha expression is significantly higher in type I than type II cells, a total of 20 primary epithelial ovarian cancer cells are used. The ratio of IKKbeta/IKKalpha expression is significantly higher in type I than type II cells. MicroRNA hsa-miR-199a regulates IKKbeta expression in epithelial ovarian cancer cells (EOC)
Manually annotated by BRENDA team
additional information
-
IKKalpha is present in the nucleus of most primary colorectal tumor tissues and CRC cell lines but not in HS27 or HEK-293 control cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
IKK complex, NEMO/IKKgamma is shuttling between cytoplasm and nucleus
Manually annotated by BRENDA team
-
IKK-beta and IKK-alpha
Manually annotated by BRENDA team
-
IKKbeta and IKKalpha are almost entirely cytoplasmic, IKK complex component scaffold protein NF-kappaB essential modulator, i.e. NEMO or IKKgamma, shuttles between the cytoplasm and the nucleus in a CRM-dependent manner
Manually annotated by BRENDA team
-
IKKalpha is located both in cytoplasm and nucleus, IKKbeta is predominantly cytoplasmic
Manually annotated by BRENDA team
-
IKKalpha is located both in cytoplasm and nucleus, IKKbeta is predominantly cytoplasmic
Manually annotated by BRENDA team
-
IKKalpha shuttles between the nucleus and cytoplasm in a CRM1-dependent fashion
Manually annotated by BRENDA team
-
NEMO/IKKgamma is shuttling between cytoplasm and nucleus
Manually annotated by BRENDA team
-
IKK complex component scaffold protein NF-kappaB essential modulator, i.e. NEMO or IKKgamma, shuttles between the cytoplasm and the nucleus in a CRM-dependent manner
Manually annotated by BRENDA team
-
nuclear accumulation of IKKalpha occurs in response to CDDP, IKKalpha shuttles between the nucleus and cytoplasm in a CRM1-dependent fashion
Manually annotated by BRENDA team
-
IKKalpha is located both in cytoplasm and nucleus, e.g. TNF-alpha, a critical pro-inflammatory cytokine, and Helicobacter pylori stimulate IKKalpha nuclear translocation, mechanisms of IKKalpha nuclear translocation, overview. Kinase activation is required for IKKalpha to translocate into the nucleus
Manually annotated by BRENDA team
-
IKKalpha is located both in cytoplasm and nucleus, e.g. TNF-alpha, a critical pro-inflammatory cytokine, cisplatin, estrogen, EGF, and Helicobacter pylori stimulate IKKalpha nuclear translocation, mechanisms of IKKalpha nuclear translocation, overview. Overexpression of Kaposi's sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein K13 and hepatitis B virus-encoded X protein also induce IKKalpha nuclear translocation to regulate NF-kappaB activity. Kinase activation is required for IKKalpha to translocate into the nucleus
Manually annotated by BRENDA team
additional information
-
treatment with ATM inhibitors blocks the nuclear IKKalpha accumulation by cisplatin, suggesting that ATM plays a role in the nuclear translocation of IKKalpha
-
Manually annotated by BRENDA team
additional information
-
treatment with ATM inhibitors blocks the nuclear IKKalpha accumulation by cisplatin, suggesting that ATM plays a role in the nuclear translocation of IKKalpha
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
700000
-
-
IKK complex
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
gel filtration
dimer
-
the IkappaB kinase complex, IKK, contains two kinase subunits, IKKalpha and IKKbeta
dimer
-
the IkappakappaB kinase complex, IKK, contains two kinase subunits, IKKalpha and IKKbeta
heterotrimer
-
IkappaB kinase, IKK, consists of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit called NEMO or IKKgamma
heterotrimer
-
IkappaB kinase, IKK, consists of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit IKKgamma, NEMO
oligomer
-
the IKK complex is built by subunits IKKalpha, IKKbeta, and IKKgamma/NEMO
oligomer
-
IKK is a large molecular weight complex consisting of at least two catalytic subunits, IKKalpha, IKKbeta, and the associated regulatory subunit IKKgamma, NEMO
oligomer
-
the IkappaB kinase complex comprises two catalytic subunits, IKK1 and IKK2, also termed IKKalpha and IKKbeta, respectively
oligomer
-
the IkappaB kinase complex is composed of two catalytic subunits, IKKalpha and IKKbeta, or IKK1 and IKK2, and a regulatory subunit, IKKgamma, NEMO or IKKAP1
oligomer
-
the multisubunit IkappaB kinase complex is composed of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit termed NEMO or IKKgamma
oligomer
-
two catalytic subunits, IKK1 and IKK2
heterotrimer
-
IkappaB kinase, IKK, is composed of two catalytic subunits, IKK1 or IKKalpha and IKK2 or IKKbeta, and a regulatory subunit called NEMO or IKKgamma
additional information
-
2-step tetrameric oligomerization of IKKgamma, mediated by C-terminal coiled-coil domains, is obligatory for IKK complex phosphorylation activity and NF-kappaB activation in vivo, the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic IKKgamma, which bind to each other independently of IKKgamma oligomerization status, overview
additional information
-
IKK complex is composed of catalytic IKK1 and IKK2, and regulatory IKKgamma, i.e. NEMO, subunits
additional information
-
IKKbeta contains a leucine zipper, a T-loop, and a HLH domain important for phosphorylation and ubiquitination, the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic, regulatory NEMO/IKKgamma
additional information
-
subunits IKK1 and IKK2
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic NEMO/IKKgamma
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic NEMO/IKKgamma
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic NEMO/IKKgamma, complexes of IKKalpha and IKKgamma or IKKalpha homodimers are not stable
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic, regulatory NEMO/IKKgamma
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic, regulatory NEMO/IKKgamma
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and regulatory IKKgamma
additional information
-
the enzyme activity is included in a complex formed of the scaffold protein NF-kappaB essential modulator, i.e. NEMO or IKKgamma, and the Ikkalpha and IKKbeta kinases, overview, the complex contains a zinc finger-like domain, N- and C-terminal coiled-coil domains, two alpha-helices and a leucine zipper
additional information
-
within its activation loop, IKKbeta and IKKalpha contain an evolutionarily conserved LxxLAP consensus motif for hydroxylation by prolyl hydroxylases, while p65, p50, IkappaBalpha, and NEMO/IKKgamma are without this sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
-
phosphoprotein
-
IKKbeta is phosphorylated at the T loop residues Ser171 and Ser181, chronic phosphorylation leads to attachment of one ubiquitin molecule at nearby Lys163, which in turn modulates the phosphorylation status at select C-terminal serines
phosphoprotein
-
subunit IKKgamma is activated by phosphorylation via IKKbeta subunit at Ser31, Ser43, and Ser376, IKKgamma phosphorylation requires its zinc finger sequence at the C-terminus, phosphopeptide mapping
phosphoprotein
-
IKKbeta is activated by phosphorylation at Ser171 and Ser181 of the activation loop
phosphoprotein
-
activation of IKKbeta requires phosphorylation on Ser177/Ser181 of its active loop. 17-acetoxyjolkinolide B increases the phosphorylation of IKKbeta
phosphoprotein
-
human leukemia virus type-1 TAX-mediates IkappaB phosphorylation
phosphoprotein
-
IL-1 induces phosphorylation of IKKalpha on the NFkappaB inducing kinase (NIK) phosphorylation sites Ser176/Ser180 and on the Thr23 site
phosphoprotein
-
knockdown of either mTOR or raptor in PC3 cells induces phosphorylation of IKKalpha and IKKbeta in their activation loops
phosphoprotein
-
treatment with TNF-alpha induces a time-dependent increase in phosphorylated IKKbeta in Type I EOC cells but not in Type II EOC cells. No changes are observed for IKKalpha in either cell type
phosphoprotein
-
ATM activates and phosphorylates IKKalpha at Ser473 in an in vitro kinase assay
phosphoprotein
-
the IkappaB complex gets activated by phosphorylation and then autophosphorylates IkappaBalpha at Ser32 and Ser36
phosphoprotein
P33973
autophosphorylation at both Ser and Thr
phosphoprotein
-
-
additional information
-
within its activation loop, IKKbeta contains an evolutionarily conserved LxxLAP consensus motif for hydroxylation by prolyl hydroxylases
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cytoplasmic extracts are prepared
-
native IkappaBalpha kinase from HeLa S3 cells by ammonium sulfate fractionation, ultrafiltration, and gel filtration
-
nuclear and cytoplasmic extracts are prepared
-
recombinant C-terminally FLAG-tagged wild-type and mutant IKK-2s
-
recombinant GST-fusion IKKgamma protein from Escherichia coli strain BL21 by glutathione affinity and anion exchange chromatography, and gel filtration, recombinant His-tagged IKKgamma protein from Escherichia coli strain BL21 by nickel affinity chromatography
-
recombinant His-tagged IKKbeta from Sf21 insect cells by nickel affinity chromatography
-
using Ni-NTA-chromatography
-
GST-fusion protein are purified with glutathione sepharose 4B
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
a Flag-tagged IKKbeta expression vector is used
-
a GST-IkappaBalpha fusion protein is generated; a GST-IkappaBalpha fusion protein is generated
-
coexpression of FLAG-atgged wild-type and mutant IKKbeta proteins with T7-tagged IKKgamma and HA-tagged ubiquitin in 293T cells
-
coexpression of FLAG-tagged IKKbeta, T7-tagged IKKgamma, and Tax in 293T cells and in murine embryonic fibroblasts devoid of the enzyme
-
coexpression of HA-tagged IKKbeta and GST-fusion IKKgamma in 293 cells, expression of GST-fusion or His-tagged IKKgamma protein in Escherichia coli strain BL21
-
coexpression of Myc-tagged NEMO/IKKgamma, FLAG-tagged p65, and HA-tagged or GST-tagged CREB-binding protein in 293T cells or in mouse embryonic fibroblasts MEF cell line
-
expressed in baculovirus-infected Sf9 cells
-
expressed in baculovirus-infected sf9 insect cells
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expression of C-terminally FLAG-tagged wild-type and mutant IKK-2s
-
expression of FLAG- or HA-tagged wild-type and mutant IKKbeta in HEK-293 and HeLa cells
-
expression of GST-tagged IKKalpha and IKKbeta in HEK-293 cells, coexpression of IKKbeta and GFP-tagged DELTANp73alpha protein in HEK-293 cells
-
expression of mutant IKKbeta and IKKalpha in HeLa cells and in HEK293 cells, expression of His-tagged IKKbeta in Spodoptera frugiperda Sf21 cells via baculovirus infection
-
expression of Myc-tagged IKK-alpha or IKK-beta in mouse embryonic fibroblasts MEF cell line
-
expression of wild-type FLAG-tagged IKK-beta or FLAG-tagged IKK-beta mutant C179A in A-293 cells
-
Flag-IKKalpha and Flag-IKKbeta vectors for transfection of HEK293 cells are used
-
IKKalpha, IKKbeta and IKKgamma, cloned into pRK-FLAG or pRK-HA, are used, IKKbeta fragments, aa1-398, aa399-576, aa577-756, are inserted into the vector pRK-FLAG
-
into the vector pSC-b for sequencing, subsequently into pCMV-FLAG-1 or pEBG6P
-
recombinant human IKK-beta, residues 1-737, is expressed in Baculovirus as a C-terminal GST-tagged fusion protein, a 6-His-tagged full length IKK-alpha construct is used
-
transient coexpression of IKKepsilon, IRF3, and TBK1 or IKKbeta in 293T cells, transient coexpression of IFN-beta or ISRE reporter genes and IKKepsilon or TBK1 in HEK293 cells with or without FLAG or GFP tag
-
transient expression of HA-tagged IKKalpha, IKKbeta, and IKKalpha mutant L605R/F606P in Jurkat cells, transient coexpression of myc-tagged Vav-1 and IKKalpha in Jurkat cells
-
transient expression of wild-type and mutant FLAG-tagged IKK2 in HELF cells
-
transient expression of wild-type and mutant IKKbeta in HeLa cells
-
adenoviral-mediated transient IKKbeta expression in enzyme-deficient cells significantly reduces apoptosis of the cells in response to arsenic
-
expression of FLAG-tagged wild-type and mutant enzymes in HEK-293 and HeLa cells, expression of the C-terminal fragment, comprising amino acids 541-716, of IKKepsilon with NF-kappaB2/p100/p52 in yeast two-hybrid cells
-
expression of IKKalpha in COS-7 cells, co-expression with p73alpha and His-tagged ubiquitin, analysis of ubiquitinated compounds
-
expression of IKKbeta in the yeast two-hybrid system, interaction with epithelial sodium channel alphabetagamma-ENaC, coexpression of IKKbeta and alphabeta-FLAG-gamma-ENaC in Xenopus laevis oocytes increases amilorid-sensitive current
-
expression of Myc-tagged IKK-alpha or IKK-beta in embryonic fibroblasts MEF cell line
-
expression of the enzyme using the baculovirus transfection method in HEK-293 cells
-
IKKbeta DNA fragments encoding the region covering the RelB-transactivation domain containing a putative leucine zipper motif, aa301-540, or helix-loop-helix and NEMO-binding domain, aa541-757, are inserted into pBHA and used as baites to screen a cDNA library, to express GST-fusion proteins in Escherichia coli, the gene fragments aa1-300, aa301-540, and aa541-756 are inserted into pGEX4T-1 or pCDNA3HA, all IKKbeta constructs, full length, aa1-300, aa301-757, aa1-540, and aa301-540-deleted forms, and IKKalpha are inserted into pCMV2-FLAG plasmids
-
IKKepsilon expression analysis
-
overexpression of a gain-of-function mutant of IKK2, IKK2-EE or IKK2CA, in transgenic mice pancreas using an inducible genetic tet system, the mice additionally overexpress CMV-rtTA protein, overview
-
overexpression in Escherichia coli
P33973
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
IKKalpha and IKKbeta downregulation in 38E6E7HFK cells by siRNA expression
-
LRRK2 phoshorylation is not induced by activation of the MyD88 pathway
-
Zymosan induces LRRK2 phosphorylation at S395 by IKK, stimulation of the Toll-like receptor pathway by MyD88-dependent agonists in bone marrow-derived macrophages or RAW264.7 macrophages induces IKK
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C179A
-
site-directed mutagenesis of IKKbeta at the activation loop, the mutant shows reduced activation and activity compared to the wild-type enzyme, which is not restorable by TNF stimulation, activity of the mutant is partially recovered when its phosphorylation is enforced by coexpression with mitogen-activated protein kinase kinase kinases such as NF-kappaB inducing kinase, NIK, and MAPK/extracellular signal-regulated kinase kinase kinase 1, MEKK1, or when the serine residues are replaced with phospho-mimetic glutamate, the mutant is normal in dimer formation, while its activity abnormally responds to the change in the concentration of substrate ATP, overview
C179A
-
berberine does not have any effect on mutant IKK beta C179A. This proves that berberine inhibits IKK beta activity through the modification of Cys179
C179A
-
mutant, not susceptible to the inhibitor N-tosyl-L-phenylalanine chloromethyl ketone
D145A
-
site-directed mutagenesis, the IKK-2 is devoid of kinase activity despite its ability to bind ATP with high affinity and is not phosphorylated at the T loop. mutant binds a diverse collection of inhibitors with comparable binding affinities to wild-type IKK-2, inhibition by PHA-408 is reduced compared to the wild-type enzyme
DELTA1-640
-
deletion mutant containing residues 640-756, which contains the entire C-terminal region after the HLH domain, interacts well with NEMO
DELTA1-680
-
deletion mutant wich stably interacts with NEMO
DELTA1-705
-
deletion mutant comprising just the predicted alpha-helical and coiled-coil region and the NEMO binding domain (NPD) residues 734-745 is sufficient for a stable interaction with NEMO
DELTA1-734
-
deletion mutant containing only the 11-residues of the NEMO-binding region (NBD) is not sufficient for interaction with NEMO
DELTA307-384
-
mutant protein consisting of a deletion of the ubiquitin-like domain that is present only in IKKbeta fails to activate NFkappaB in response to IL-1 or TNF. Deletion mutant is incorporated into the IKK complex, indicating that this domain is not important for the intermolecular interaction between the IKKs and NEMO. Deletion mutant strongly associate with the NF-kappaB p65 subunit in the absence or presence of stimuli, whereas wild-type IKKbeta can not be detected in a complex with p65. This indicates that the to propose a model in which the ubiquitin-like domain plays a role in release of NF-kappaB following IkappaBalpha phosphorylation
DELTA395-756
-
mutant lacking the leucine zipper domain, the helix-loop-helix domain, the serine rich and the NEMO-binding motif are capable to catalyze phosphotransfer to the substrate protein IkappaBalpha, but they do so at positions outside Ser-32 and Ser-36 while leaving these two critical amino acids unmodified. Removal of the leucine zipper and helix-loop-helix regions converts IKKbeta to monomer
DELTA395-756D145N
-
mutant lacking the leucine zipper domain, the helix-loop-helix domain, the serine rich and the NEMO-binding motif and containing a Asp145Asn mutation does not display any kinase activity
DELTA665-756
-
mutant lacking the serine rich and the NEMO-binding motif retains the ability to phosphorylate its substrate IkappaBalpha exclusively at serine positions 32 and 36
F26A
-
site-directed mutagenesis, the mutant has lost the time-dependent binding of inhibitor PHA-408
F26W
-
site-directed mutagenesis
K106N
-
site-directed mutagenesis
K106Q
-
site-directed mutagenesis, the mutant shows time-dependent inhibition like the wild-type, inhibition by PHA-408 is slightly increased compared to the wild-type enzyme
K106R
-
site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta
K147R
-
site-directed mutagenesis, reduced monoubiquitination of IKKbeta mutant
K163R
-
site-directed mutagenesis, monoubiquitination-defective mutant of IKKbeta retaining kinase activity in Tax-expressing cells
K171R
-
site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta
K18R
-
site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta
K198R
-
site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta
K234R
-
site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta
K238R
-
site-directed mutagenesis, monoubiquitination-defective mutant of IKKbeta
K254R
-
site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta
K275R
-
site-directed mutagenesis, ubiquitination and phosphorylation of the mutant is unaltered compared to the wild-type IKKbeta
K44A
-
site-directed mutagenesis of subunit IKK2, catalytically inactive mutant and no NF-kappaB stimulation in infected cells in vivo
K44M
-
site-directed mutagenesis, inactive IKKalpha mutant, site-directed mutagenesis, inactive IKKbeta mutant
K44M
-
a kinase-dead mutant of IKKalpha
K44R
-
site-directed mutagenesis, monoubiquitination-defective mutant of IKKbeta
L353X
-
L353 within the ubiquitin-like domain is necessary to activate NF-kappaB-dependent gene expression. However, the L353 mutant is able to phosphorylate IkappaBalpha suggesting that the defect in NF-kappaB activation is not at the level of inhibition of IkappaB degradation
L605R/F606P
-
IKKalpha mutant, defective in HLH domains, unable to bind wild-type Vav-1
P191A
-
inactive IKKbeta mutant
S176E/S180E
-
vaccinia virus virulence factor B14 does inhibit a mutant containing a mutation in the activation loop. This suggests that phosphorylation of these serine residues in the activation loop of IKKbeta is targeted by B14
S177E/S181E
-
ectopic overexpression of a constitutively active form of IKKbeta in Type II epithelial ovarian cancer cells (EOC) results in a significant decrease in IkappaBalpha expression
S177E/S181E
-
vaccina virus virulence factor B14 does not inhibit a mutant containing a mutation in the activation loop. This suggests that phosphorylation of these serine residues in the activation loop of IKKbeta is targeted by vaccina virus virulence factor B14
T23A
-
overexpression of a Ikappa B kinase alpha mutant, IKKalphaT23A, containing a mutation in a functional AKT phosphorylation site, completely abrogate IL-6 promoter activation in response to IL-1
Y169F
-
site-directed mutagenesis, the mutant shows time-dependent inhibition by PHA-408 like the wild-type
K38A
-
inactive IKKepsilon mutant
K44A
-
inactive IKKbeta mutant
K44M
-
gene transfer of a dominant negative (kinase-dead form) IKKbeta into rat soleus muscles show complete inhibition of 7-day disuse-induced activation of a kappaB reporter gene, while overexpression of wild-type IKKbeta does not. Overexpression of a dominant-negative mutant IKKbeta-EGFP fusion protein show that atrophy is inhibited by 50%, indicating that IKKbeta is required for the atrophy process
K44M
-
overexpression of a dominant negative (kinase-dead form) IKKbeta plus dominant-negative IKKalpha show an additive effect on the inhibition of disuse atrophy (70%), suggesting that both kinases of the IKK complex are required for muscle atrophy
K44M
-
overexpression of a dominat-negative (kinase-dead form) of the IKKalpha protein decreases unloading-induced NF-kappaB activation and inhibits atrophy by 50%, while overexpression of the wild-type protein has no effect
S176E/S180E
-
overexpression of a constitutively active IKKalpha-EGFP fusion protein shows that IKKalpha is sufficient to activate NF-kappaB activity and induce fiber atrophy in muscle
S177E/S181E
-
overexpression of a constitutively active IKKbeta-EGFP show a marked increase in NF-kappaB activity and a decrease in fiber size of weight-bearing soleus muscles, while muscles overexpressing wild-type IKKbeta-HA have no effect
M96L
-
site-directed mutagenesis
additional information
-
construction of IKKgamma peptide fragements and sequence deletion mutants for determination of intermolecular interaction of IKKgamma required for 2-step tetramerization, overview
additional information
-
IKKepsilon and TBK1 interference RNA blocks IRF3 activation
additional information
-
mutations of X-linked gene encoding IKKgamma can lead to immunodeficiency diseases interfering with NFkappaB-signaling
additional information
-
IKK subunit-specific small interfering RNAs and cells deficient in individual IKK subunits show that IKKalpha subunit, not IKKbeta, is required for reovirus-induced NF-kappaB activation and apoptosis, overview, NF-kappaB activation and apoptosis are delayed in cells deficient in the IKK complex components IKKgamma/NEMO, overview
additional information
-
analysis of IKKalpha and IKKbeta knockout cells shows that IKK alpha is the critical IKK subunit in controlling insulin-induced interaction with mTOR
additional information
-
ectopic expression of IKKbeta in epithelial ovarian cancer cells (EOC) induces cytokine production in Type II EOC cells
additional information
-
enhanced IKKalpha expression increases both early and terminal differentiation of human keratinocytes through an E-cadherin-dependent mechanism
additional information
-
expression of IKKalpha or IKKbeta is ablated in primary human chondrocytes by retrotransduction of specific short-hairpin RNAs. Micromass cultures designed to reproduce chondrogenesis with progression to the terminal hypertrophic stage are established, and anabolism and remodeling of the extracellular matrix (ECM) are investigated in the micromasses. Ablation of IKKalpha dramatically enhance type II collagen deposition independent of SOX9 protein levels but in association with suppressed levels of runt-related transcription factor 2. IKKalpha-deficient cells retain the phenotype of cells in a pre-hypertrophic-like state, as evidenced by the smaller size and faster proliferation of these cells prior to micromass seeding, along with the enhanced viability of their differentiated micromasses, expression of IKKalpha or IKKbeta is ablated in primary human chondrocytes by retrotransduction of specific short-hairpin RNAs. Silencing of IKKbeta markedly enhances accumulation of glycosaminoglycan in conjunction with increased SOX9 expression
additional information
-
in cells infected with vaccina virus lacking gene B14R there is a higher level of phosphorylated IkappaBalpha but a similar level of IkappaBalpha compared to cells infected with control viruses expressing vaccina virus virulence factor B14, suggesting vaccina virus virulence factor B14 affects IKK activity, in cells infected with vaccinia virus lacking gene B14R there is a higher level of phosphorylated IkappaBalpha but a similar level of IkappaBalpha compared to cells infected with control viruses expressing vaccinia virus virulence factor B14, suggesting vaccinia virus virulence factor B14 affects IKK activity
additional information
-
in HEK293 cells, knockdown of IKK alpha suppresses TNF-induced mTOR activation by greater that 50%, knockdown of IKKbeta has less of an effect
additional information
-
knockdown of IKKalpha alone or combined IKKalpha/beta causes significant loss of NF-kappaB DNA binding activity in Panc-1 cells. The suppressive effects of IKKalpha and combined IKKalpha/beta knockdown are stronger than IKKbeta knockdown alone, knockdown of IKKalpha and IKKbeta by RNAi leads to a significant reduction of Panc-1 cell and MiaPaCa-2 cell growth
additional information
-
siRNA-directed knockdown of Akt2 in PC3 cells leads to dissociation of IKKalpha from the mTOR (mammalian target of rapamycin) complex
additional information
-
using siRNA to IKKalpha it is shown that IKKalpha is required for efficient induction of mTOR activation in response to insulin or TNF. Knockout of IKKalpha significantly reduces insulin- or TNF-induced activation
additional information
-
a vector expressing a mutant form of IKK2 is used, characterized by the substitution of two serine residues with alanines, leading to inhibition of IKK2 autophosphorylation required for IKK activity
additional information
-
overexpressing a dominant-negative mutant of IKKbeta in 38E6E7HFK cells results in reduced levels of phospho-IkappaBalpha and a decrease in DELTANp73alpha protein levels, while no significant changes in DELTANp73alpha mRNA levels are observed
K44A
-
site-directed mutagenesis, inactive ATP-binding site mutant, the kinase-deficient mutant IKK-alpha fails to stabilize p73
additional information
-
construction of IKK knockout mice as a model system for drug development
additional information
-
construction of IKKalpha-deficient and of IKKbeta-deficient mice and BM cell mutants, the mutants show defective osteoclastogenesis, wild-type osteoblasts can rescue osteoclastogenesis in IKKalpha- and IKKbeta-defective mutant BM cells, exogenic TNFalpha can rescue only IKKalpha-deficient mutants, TNFR1 can rescue IKKbeta-deficient osteoclast progenitors, but not prevent TNFalpha-induced apoptosis, overview
additional information
-
disruption of the gene encoding IKKbeta leads to apoptotic tissue damage, e.g. in mucosa, and prevention of systemic inflammatory response, which results in the multiple organ dysfunction syndrome MODS
additional information
-
IKKbeta-deficient B-cells are impaired in mitogenic responses to lipopolysaccharides, anti-CD40, and anti-IgM, and show high reduction of all peripheral B-cell subsets due to associated defects in cell survival
additional information
-
disruption of Ikbke-/-, the gene encoding IKKepsilon, results in a complete loss of the kinase in both mice and embryonic fibroblasts, generation of mice lacking IKKepsilon, the mice produce normal amounts of IFNbeta, but are hypersusceptible to viral infection because of a defect in the IFN signaling pathway, phenotype, overview
additional information
-
fibroblasts of ikkbeta-/- mice exhibit enhanced apoptosis in response to TNFalpha, NEMO/IKKgamma-deficient mice shows a phenotype with liver damage, but can be rescued by inactivation of the gene encoding the tumor necrosis factor-1, phenotypes, overview
additional information
-
generation of IKKalpha-/- mice, an autoimmune disease phenotype is induced in athymic nude mice by grafting embryonic thymus from IKKalpha-deficient mice
additional information
-
IKK knockout mice show downregulation of the CBM complex components Carma1 and Malt1, and impaired degradation of IkappaBalpha, overview
additional information
-
IkkalphaAA/AA 'knockin' mice, in which activation of IKKalpha is prevented by replacement of activation loop serines with alanines, exhibit delayed mammary gland growth during pregnancy, because IKKalpha activity is required for cyclin D1 induction and proliferation of lobuloalveolar epithelial cells, overview, retarded tumor development in response to either 7,12-dimethylbenzaanthracene or the ErbB2/Her2 transgene but had no effect on MMTV-v-Haras-induced cancer, overview
additional information
-
IKKbeta-/- 3T3 fibroblasts show decreased expression of antioxidant genes, such as metallothionein 1, Mt1, IKKbeta null cells display a marked increase in arsenic-induced reactive oxygen species accumulation, which leads to activation of the MKK4-c-Jun NH2-terminal kinase pathway, c-Jun phosphorylation, and apoptosis, overview
additional information
-
small interfering RNA-mediated knockdown of endogenous IKK-alpha inhibits the CDDP-mediated accumulation of p73alpha, the kinase-deficient mutant form of IKK-alpha interacts with p73alpha, but fails to stabilize it, CDDP-mediated accumulation of endogenous p73alpha is not detected in mouse embryonic fibroblasts prepared from IKK-alpha-deficient mice, and CDDP sensitivity is significantly decreased compared to wild-type MEFs, overview
additional information
-
TLR7/9-induced IFN-alpha production is severely impaired in constructed IKK-alpha-deficient plasmacytoid dendritic cells, whereas inflammatory cytokine induction is decreased but still occurrs, kinase-deficient IKK-alpha inhibits the ability of MyD88 to activate the Ifna promoter in synergy with IRF-7, expression of kinase-deficient IKK-alpha does not affect IRF-7-mediated promoter activation, but inhibits the enhancing effects ofMyD88
additional information
-
transfection of siRNA duplexes directed against IKKi and TBK1 downregulates the expression levels of both kinase isoforms by about 70%
additional information
-
conditional IKKbeta knockout mice are used in which the IKKbeta gene is specifically deleted in cells of myeloid lineage, including microglia, in the CNS. This deletion reduced IkappaB kinase (IKK) activity in cultured primary microglia by up to 40% compared with wild-type. Kainic acid-induced hippocampal neuronal cell death is reduced by 30% in knockout mice compared with wild-type mice
additional information
-
gene disruption via homologous recombination reveals that activation of NF-kappaB in response to pathogen associated molecular patterns (PAMPs) and pro-inflammatory cytokines is dependent on IKKgamma/NEMO and on IKKbeta, gene disruption via homologous recombination reveals that IKKalpha, but not IKKbeta, kinase activity is required for activation of an alternative NF-kappaB signaling pathway based on processing of NF-kappaB2/p100:RelB complexes to NF-kappaB2/p52:RelB dimers. In addition, IKKalpha, and not IKKbeta, is required for differentiation of stratified epithelia, such as the epidermis, but this function does not require its protein kinase activity, Ikkalpha knockin mice are generated in which the two serine phosphoacceptor sites responsible for kinase activation are replaced with alanines. These mice express normal amounts of an IKKalpha protein whose kinase activity cannot be turned on in response to upstream stimuli. TRAMP mice, a mouse model for prostate carcinoma, that are rendered homozygous for the Ikkalpha knockin mutation are found to exhibit decelerated tumor development but eventually all died of primary prostate carcinoma. Knockin mice are found to display much fewer secondary site metastases than wild-type/TRAMP mice, indicating that IKK alpha is an enhancer for prostate metastasis
additional information
-
IKKbeta knock-out mice are embryonically lethal
additional information
-
increased expression of IKKalpha in mouse tumorigenic epidermal cells (PDVC57) leads to changes in the differentiation pattern of the resulting squamous cell carcinomas, originating a distinct histological variant that resembles the human acantholytic squamous cell carcinomas (ASCC) variant
additional information
-
knock-out mice are generated lacking IKK1, IKK2, NEMO(IKKgamma), or both IKK1 and IKK2 in liver parenchymal cells: IKK1 and IKK2 ablation, sensitizes the liver to in vivo LPS challenge, uncovering a redundant function of the two IkappaB kinases in mediating canonical NF-kappaB signaling in hepatocytes and protecting the liver from TNF-induced failure. Knock out mice with combined ablation of IKK1 and IKK2 or IKK1 and NEMO spontaneously develop severe jaundice and fatal cholangitis characterized by inflammatory destruction of small portal bile ducts
additional information
-
mice lacking the beta subunit of IKK in myeloid cells are more susceptible to endotoxin shock than control mice, which might be a serious challenge for long-term IKKbeta inhibition
additional information
-
mice lacking the IKKbeta gene in hepatocytes surprisingly show many more and faster growing chemically-induced hepatocellular carcinoma, indicating that in hepatocytes IKKbeta inhibits chemically-induced hepatocellular carcinoma, targeted gene disruption of IKKbeta in intestinal epithelial cells leads to a 80% decline of colitis-associated cancer (CAC) induced by azoxymethane or dextran sulfate sodium salt administration, targeted gene disruption of IKKbeta in mature macrophages and neutrophils leads to a 50% decrease of tumor multiplicity of colitis-associated cancer (CAC) induced by azoxymethane or dextran sulfate sodium salt administration
additional information
-
using IKKbeta MCF7 knockout cells it is shown that in MCF7 cells TNF does not activate Akt and requires IKKbeta to activate mTOR
additional information
A1L361
using TBK1-deficient mice it is shown by bone-marrow transfer experiments that TBK1-mediated signalling in haematopoietic cells is critical for the induction of antigen-specific B and CD41 T cells, whereas in non-haematopoietic cells TBK1 is required for CD81 T-cell induction, using TBK1-deficient mice it is shown that TBK1 mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice. Plasmid-DNA-activated, TBK1-dependent signalling and the resultant type-I interferon receptor-mediated signalling is required for induction of antigen-specific B and T cells, which occurred even in the absence of innate immune signalling through a well known CpG DNA sensor—Toll-like receptor 9 (TLR9) or Z-DNA binding protein 1
additional information
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generation of knock-in mice that express a mutant form of IKKalpha that cannot be activated, i.e. IKKalphaAA
S177E/S181E
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site-directed mutagenesis, gain-of-function mutant of IKK2, IKK2-EE or IKK2CA, the mutant ICC2CA in pancreatic acinar cells increases tissue damage of secretagogue induced experimental pancreatitits, overview
additional information
Mus musculus C57BI/6J
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disruption of the gene encoding IKKbeta leads to apoptotic tissue damage, e.g. in mucosa, and prevention of systemic inflammatory response, which results in the multiple organ dysfunction syndrome MODS
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APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
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because of its central role in the overall NF-kappaB regulation, IKK-2 is a viable target for drug discovery
medicine
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IKK activates TNFalpha-dependent signaling pathways inducing drug resistance, e.g. increasing cell survival in anti-cancer treatment with 5-fluoro-2'-deoxyuridine, overview
medicine
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inhibition of IKK-driven NF-kappaB activation offers a strategy for treatment of different malignancies and can convert inflammation-induced tumor growth to inflammation-induced tumor regression
medicine
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17-acetoxyjolkinolide B is a novel type NF-kappaB pathway inhibitor. Its unique interaction mechanism with IKK may render it a strong apoptosis inducer of tumor cells and a novel type anticancer drug candidate
medicine
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IKKalpha is responsible for the development of acantholytic squamous cell carcinoma (ASCC), a human SCC variant
medicine
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IKK is thought to be a focal target of drug development
medicine
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IKK2 inhibition represents a promising strategy for the treatment of advanced stages of cutaneous T-cell lymphomas
medicine
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IKKbeta inhibitors are utilized for the treatment of cancer and immunological disorders
medicine
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inhibition of IkappaB kinase beta restrains oncogenic proliferation of pancreatic cancer cells
medicine
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inhibitors of IKK2 could be effective in the treatment of autoimmune and inflammatory disorders such as rheumatoid arrthritis, inflammatory bowel disease, lupus and multiple sclerosis
medicine
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N-tosyl-L-phenylalanine chloromethyl ketone has been shown to have therapeutic effects in hypoxic-ischemic brain injury and collagen-induced arthritis in experimental animals, without any obvious adverse side effects
medicine
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PHA-408 is efficacious in a chronic model of arthritis with no adverse effects
medicine
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since IKK2 is vital for translating pro-inflammatory stimuli into the activation of NF-kappaB, an inhibitor of IKK2 could be effective in the treatment of autoimmune and inflammatory disorders
molecular biology
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IKKalpha and IKKbeta exert differential roles in ECM remodeling and endochondral ossification, which are events characteristic of hypertrophic chondrocytes and also complicating factors often found in osteoarthritic chondrocytes
molecular biology
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it is shown that mTOR and Raptor, through an Akt-dependent pathway, control NF-kappaB activity in PC3 prostate cancer cells both at the level of IkappaBalpha and RelA/p65 phosphorylation
molecular biology
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NF-kappaB is activated by alloferon through down-regulation of antioxidant proteins and IkappaBalpha
molecular biology
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regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells
pharmacology
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enzyme is a target for development of inhibitors of HIV-1 replication, overview
pharmacology
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IKK ia a good target for development of anti-rheumatic and anti-inflammatory drugs
pharmacology
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IKK is a target for development of therapeutics for treatment of diseases resulting from nuclear transcription factor NFkappaB pathogenesis
pharmacology
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IKKbeta/NF-kappaB inhibitors can be useful adjuvants for conventional chemotherapeutic drugs, ionizing radiation, or tumoricidal cytokines, e.g. IFNs or TRAIL
pharmacology
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aberrant kinase activity is implicated in many diseases and makes this target class attractive for the pharmaceutical industry
medicine
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Helicobacter pylori-mediated gastric inflammation critically depends on the efficient recruitment and activation of macrophages, with sufficient NF-kappaB activation
analysis
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development of real-time imaging for continous enzyme detection and kinetics in intact cells and living mice utilizing a recombinant IkappaBalpha-firefly luciferase reporter construct, system can be used for determination of kinetics/pharmacodynamics of potential selective inhibitors, and for investigations of NF-kappaB signalling pathway activation
medicine
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IKKlapha may represent a specific target for treatment of ErbB2-positive breast cancer
medicine
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results reveal a novel function of the two IkappaB kinases in cooperatively regulating liver immune homeostasis and bile duct integrity and suggest that IKK signaling may be implicated in human biliary diseases
medicine
A1L361
TBK1 is a key signalling molecule for DNA-vaccine-induced immunogenicity, by differentially controlling DNA-activated innate immune signalling through haematopoietic and non-haematopoietic cells
medicine
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IKKbeta-targeted NF-kappaB blockade is an attractive therapeutic approach for the prevention of colitis-associated tumors
medicine
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inhibition of IkappaB kinase beta induces growth suppression and death in cells expressing wild-type, Imatinib-resistant, or the T315I Imatinib/Dasatinib-resistant forms of BCR-ABL
medicine
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inhibition of IkappaB kinase beta restrains oncogenic proliferation of pancreatic cancer cells
molecular biology
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IKK-alpha is a potential target for manipulating TLR-induced IFN-alpha production
molecular biology
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IKK/nuclear factor-kappaB dependent microglia activation contributes to KA-induced hippocampal neuronal cell death in vivo through induction of inflammatory mediators
medicine
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the IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy
medicine
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PHA-408 is efficacious in a chronic model of arthritis with no adverse effects
medicine
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the IKKbeta/IKK2 inhibitor PHA-408 is a powerful anti-inflammatory agent against LPS- and cigarette smoke-mediated lung inflammation
medicine
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the role of IKK-2 in regulating NF-kappaB signaling in resonse to proinflammatory stimuli has made IKK-2 a primary anti-inflammation therapeutic target
molecular biology
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tetrandrine suppresses LPS-induced astrocyte activation via modulating IKKs-IkappaBalpha-NF-kappaB signaling pathway