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Information on EC 2.7.11.21 - polo kinase
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2.7.11.21 polo kinaseIUBMB Comments
The enzyme associates with the spindle pole during mitosis and is thought to play an important role in the dynamic function of the mitotic spindle during chromosome segregation. The human form of the enzyme, Plk1, does not phosphorylate histone H1, enolase and phosvitin but it can phosphorylate myelin basic protein and microtubule-associated protein MAP-2, although to a lesser extent than casein .
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Word Map
- 2.7.11.21
-
mitotic
- centrosome
-
checkpoint
-
cytokinesis
-
aurora
- microtubule
-
anaphase
- sirnas
-
polo-box
- cyclin
- kinetochore
-
cyclin-dependent
-
exit
- centriole
-
interphase
-
chromatid
-
metaphase
-
cell-cycle
-
meiosis
-
m-phase
-
faithful
-
aneuploidy
-
anaphase-promoting
-
pericentriolar
-
prometaphase
- cohesins
-
prophase
-
centromeres
- cdc25c
-
midbody
-
mitosis-specific
-
atp-competitive
- bubr1
-
kinetochore-microtubule
-
misalign
- midzone
- diagnostics
- pharmacology
-
missegregation
-
microtubule-organizing
-
monopolar
- securin
- wee1
- drug development
- cdc14
- analysis
-
condensin
-
metaphase-anaphase
- medicine
- gamma-tubulin
-
furrow
- mps1
- separase
- chk1
-
telophase
The enzyme appears in viruses and cellular organisms
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
polo-like kinase 1, polo-like kinase, plk-1, polo kinase, polo-like kinase 4, polo-like kinase-1, tbplk, plk1 kinase, cdc5p, polo-like kinase 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Plk1
-
661586, 662420, 663203, 677343, 678284, 678324, 679094, 679095, 679108, 679362, 680011, 680773, 680810, 682486, 682562, 682567, 693194, 702558, 702943, 703011, 703018, 703030, 703103, 703224, 704076, 704521, 705070, 705692, 705801, 706460, 706517, 727163, 727936, 728024, 739963, 740152, 741007, 760695, 760980, 762085
Polo-like kinase 1
-
662420, 663203, 677343, 678284, 678324, 679095, 679108, 679362, 680011, 680773, 680810, 682486, 682562, 682567, 693194, 694505, 702558, 703011, 703018, 703030, 703103, 703224, 704076, 704521, 705070, 705078, 705692, 705801, 706460, 706517, 726683, 727147, 727163, 727936, 739963, 740124, 740152, 760695, 760980
FGF-inducible kinase
-
-
-
-
Proliferation-related kinase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (spindle-pole-dependent)
The enzyme associates with the spindle pole during mitosis and is thought to play an important role in the dynamic function of the mitotic spindle during chromosome segregation. The human form of the enzyme, Plk1, does not phosphorylate histone H1, enolase and phosvitin but it can phosphorylate myelin basic protein and microtubule-associated protein MAP-2, although to a lesser extent than casein [2].
CAS REGISTRY NUMBER
COMMENTARY
149433-93-2
Polo kinase
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + Brd4
ADP + phosphorylated Brd4
the E2 binding domain of Brd4 is phosphorylated by Plk1 in vitro
-
-
?
ATP + centromeric protein PBIP1
ADP + phosphorylated centromeric protein PBIP1
Plk1 phosphorylates PBIP1 at T78, GST-PBIPtide is used as in vitro substrate
-
-
?
ATP + cJun peptide
ADP + phosphorylated cJun peptide
strong preference of PLK1 versus PLK2 and PLK3
-
-
?
ATP + gammaBD of IKKbeta
ADP + phosphorylated gammaBD of IKKbeta
Plk1 phosphorylates serines 733, 740 and 750 in the IKKgammaNEMO-binding domain, gammaBD, of IKKbeta
-
-
?
ATP + HsCdc14A
ADP + phosphorylated HsCdc14A
HsCdc14A binds to PLK1 via its C-terminus, phosphorylation partially releases the auto-inhibition of HsCdc14A, PLK1-mediated phospho-regulation promotes HsCdc14A phosphatase activity
-
-
?
ATP + p53
ADP + phosphorylated p53
Plk1 apparently phosphorylates other residues than Plk3
-
-
?
ATP + Plk1 polo box 1-derived peptide
ADP + phosphorylated Plk1 polo box 1-derived peptide
synthetic substrate
-
-
?
ATP + PLKtide
ADP + phosphorylated PLKtide
substrate corresponds to the consensus sequence for positions -7 to +6 supplemented with residues from Cdc25C for positions -23 to -8. PLK1 displays greatly enhanced activity and a strong preference for the residue corresponding to Ser198 in the optimized substrate
-
-
?
ATP + protein MAVS
ADP + phosphorylated protein MAVS
phosphorylation of the mitochondria-bound adapter protein MAVS, MAVS, mitochondrial antiviral signaling
-
-
?
ATP + SCFFbw7 ubiquitin ligase
ADP + phosphorylated SCFFbw7 ubiquitin ligase
-
-
-
?
ATP + SYK tyrosine kinase
ADP + phosphorylated SYK tyrosine kinase
-
-
-
?
ATP + viral phosphoprotein P
ADP + phosphorylated viral phosphoprotein P
PLK1 directly phosphorylates viral phosphoprotein P of paramyxovirus in vitro
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
-
-
?
ATP + BubR1
ADP + phosphorylated BubR1
S676 is an in vivo Plk1 phosphorylation site in BubR1
-
-
?
ATP + BubR1
ADP + phosphorylated BubR1
BubR1 interacts with Plk1 during prometaphase, binds to the C-terminal, complete polo-box domain of Plk1
-
-
?
ATP + BubR1
ADP + phosphorylated BubR1
Plk1-BubR1 interaction is mediated by polo-box domain binding to pT620 of BubR1. S676 is a Plk1-specific phosphorylation site, site is phosphorylated during prometaphase, but dephosphorylated at metaphase upon establishment of tension between sister chromatids. Phosphorylation is not required for spindle checkpoint function but instead is important for the stability of kinetochore-microtubule interactions, timely mitotic progression, and chromosome alignment onto the metaphase plate
-
-
?
ATP + Cdc25C
ADP + phosphorylated Cdc25C
preferentially phosphorylates Ser 198 and 191
-
-
?
ATP + Cdc25C
ADP + phosphorylated Cdc25C
the polo box domain displays a similar affinity for non-phosphorylated and phosphorylated Cdc25C target peptides, full-length Plk1 shows ca. 7fold more affinity for the phosphorylated peptide
-
-
?
ATP + Pin1
ADP + phosphorylated Pin1
Plk1-mediated phosphorylation at Ser65 stabilizes Pin1 by inhibiting its ubiquitination in cells
-
-
?
ATP + Pin1
ADP + phosphorylated Pin1
recombinant isomerase Pin1 expressed in Escherichia coli, phosphorylation at Ser65, wild-type and truncated mutant Pin1 comprising residues 1-70
-
-
?
additional information
?
-
expression of PLK mRNA appeared to be strongly correlated with the mitotic activity of cells
-
-
?
additional information
?
-
Plk1 is likely to function in cell cycle progression
-
-
?
additional information
?
-
Plk1 depletion induces apoptosis in cancer cells and stabilizes p53 tumor-suppressor protein
-
-
?
additional information
?
-
the enzyme plays an essential role in promoting mitosis and cytokinesis, the kinase activity is regulated by the conserved C-terminal polo box domain which acts as both an autoinhibitory domain and a subcellular localization domain, structure analysis
-
-
?
additional information
?
-
-
the enzyme plays an essential role in promoting mitosis and cytokinesis, the kinase activity is regulated by the conserved C-terminal polo box domain which acts as both an autoinhibitory domain and a subcellular localization domain, structure analysis
-
-
?
additional information
?
-
expanded consensus substrate sequence for PLK1
-
-
?
additional information
?
-
expanded consensus substrate sequence for PLK1
-
-
?
additional information
?
-
expanded consensus substrate sequence for PLK1
-
-
?
additional information
?
-
expanded consensus substrate sequence for PLK1
-
-
?
additional information
?
-
selective association between PLK1 and Fbw7 proteins. The WD40 domain of Fbw7 interacts with PLK1 as strongly as the full-length protein, the WD40 domain is responsible for Fbw7 association with PLK1, and the C-terminal Polobox domain (PBD), but not the N-terminal kinase domain (KD), within PLK1 selectively interacts with Fbw7 WD40 domain
-
-
?
additional information
?
-
-
selective association between PLK1 and Fbw7 proteins. The WD40 domain of Fbw7 interacts with PLK1 as strongly as the full-length protein, the WD40 domain is responsible for Fbw7 association with PLK1, and the C-terminal Polobox domain (PBD), but not the N-terminal kinase domain (KD), within PLK1 selectively interacts with Fbw7 WD40 domain
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + BubR1
ADP + phosphorylated BubR1
S676 is an in vivo Plk1 phosphorylation site in BubR1
-
-
?
ATP + Pin1
ADP + phosphorylated Pin1
Plk1-mediated phosphorylation at Ser65 stabilizes Pin1 by inhibiting its ubiquitination in cells
-
-
?
ATP + SCFFbw7 ubiquitin ligase
ADP + phosphorylated SCFFbw7 ubiquitin ligase
-
-
-
?
ATP + a protein
ADP + a phosphoprotein
-
-
-
?
additional information
?
-
expression of PLK mRNA appeared to be strongly correlated with the mitotic activity of cells
-
-
?
additional information
?
-
Plk1 is likely to function in cell cycle progression
-
-
?
additional information
?
-
Plk1 depletion induces apoptosis in cancer cells and stabilizes p53 tumor-suppressor protein
-
-
?
additional information
?
-
the enzyme plays an essential role in promoting mitosis and cytokinesis, the kinase activity is regulated by the conserved C-terminal polo box domain which acts as both an autoinhibitory domain and a subcellular localization domain, structure analysis
-
-
?
additional information
?
-
-
the enzyme plays an essential role in promoting mitosis and cytokinesis, the kinase activity is regulated by the conserved C-terminal polo box domain which acts as both an autoinhibitory domain and a subcellular localization domain, structure analysis
-
-
?
additional information
?
-
selective association between PLK1 and Fbw7 proteins. The WD40 domain of Fbw7 interacts with PLK1 as strongly as the full-length protein, the WD40 domain is responsible for Fbw7 association with PLK1, and the C-terminal Polobox domain (PBD), but not the N-terminal kinase domain (KD), within PLK1 selectively interacts with Fbw7 WD40 domain
-
-
?
additional information
?
-
-
selective association between PLK1 and Fbw7 proteins. The WD40 domain of Fbw7 interacts with PLK1 as strongly as the full-length protein, the WD40 domain is responsible for Fbw7 association with PLK1, and the C-terminal Polobox domain (PBD), but not the N-terminal kinase domain (KD), within PLK1 selectively interacts with Fbw7 WD40 domain
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(7R)-2-[5-(2,4-difluorophenyl)-1H-pyrazol-4-yl]-7-ethyl-5-methyl-8-(1-methyl-1H-pyrazol-4-yl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1-methyl-1H-pyrazol-3-yl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1-methyl-1H-pyrazol-4-yl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1-methyl-1H-pyrazol-5-yl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1H-pyrazol-4-yl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(oxetan-3-yl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-[(3S)-tetrahydrofuran-3-yl]-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-(propan-2-yl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-(pyrimidin-5-yl)-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-[(3R)-tetrahydrofuran-3-yl]-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-[(3S)-tetrahydrofuran-3-yl]-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-5-methyl-8-(1H-pyrazol-4-yl)-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-5-methyl-8-(tetrahydro-2H-pyran-4-yl)-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
-
(7R)-7-ethyl-5-methyl-8-(tetrahydrofuran-3-yl)-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
-
(7R)-8-(3,3-difluorocyclobutyl)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-7,8-dihydropteridin-6(5H)-one
-
(R)-4-[(8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl)amino]-3-methoxy-N-(1-methyl-4-piperidinyl)benzamide
i.e. BI2536
1-(1-methylpiperidin-4-yl)-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-(2-hydroxyethyl)-2-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one
-
1-(2-hydroxyethyl)-5-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1H-pyrrole-3-carboxamide
-
1-acetyl-L-prolyl-L-leucyl-3-(5-[[(Z)-([2-[acetyl(phenyl)amino]-1,3-thiazol-4-yl]methylidene)amino]oxy]pentyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-(5-[[(Z)-([2-[benzyl(methyl)amino]-1,3-thiazol-5-yl]methylidene)amino]oxy]pentyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-(5-[[(Z)-benzylideneamino]oxy]pentyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-(6-[[(Z)-([1-[4-(thiophen-2-yl)pyrimidin-2-yl]-1H-pyrrol-2-yl]methylidene)amino]oxy]hexyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-(6-[[(Z)-([2-[acetyl(phenyl)amino]-1,3-thiazol-4-yl]methylidene)amino]oxy]hexyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-(6-[[(Z)-([2-[benzyl(methyl)amino]-1,3-thiazol-5-yl]methylidene)amino]oxy]hexyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-(6-[[(Z)-([5-chloro-2-[(pyridin-2-yl)methoxy]phenyl]methylidene)amino]oxy]hexyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-(6-[[(Z)-benzylideneamino]oxy]hexyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-(8-phenyloctyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[5-([(Z)-[(2-fluoro-6-phenoxyphenyl)methylidene]amino]oxy)pentyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[6-(2-phenoxyphenyl)hexyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[6-([(Z)-[(2-fluoro-6-phenoxyphenyl)methylidene]amino]oxy)hexyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[6-([(Z)-[(4'-fluoro[1,1'-biphenyl]-2-yl)methylidene]amino]oxy)hexyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[8-(2-fluoro-6-phenoxyphenyl)octyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[8-(2-phenoxyphenyl)octyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[8-([1,1'-biphenyl]-2-yl)octyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[8-[2-(benzyloxy)phenyl]octyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-3-[9-(2-fluoro-6-phenoxyphenyl)nonyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-acetyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threoninamide
-
1-cyclohexyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-2-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one
high levels of selectivity on a panel of unrelated kinases, as well as against PLK2 and PLK3 isoforms, acceptable oral bioavailability in mice making this inhibitor a suitable candidate for further in vivo activity studies
1-methyl-5-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1H-pyrrole-3-carboxamide
high levels of selectivity on a panel of unrelated kinases, as well as against PLK2 and PLK3 isoforms, acceptable oral bioavailability in mice making this inhibitor a suitable candidate for further in vivo activity studies
1-methyl-5-(2-[[5-(piperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1H-pyrrole-3-carboxamide
-
1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid
-
1-methyl-8-[(2-methylphenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[(2-nitrophenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[(2-phenoxyphenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[(2-sulfamoylphenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[(3-nitrophenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[(4-nitrophenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[2-(methylamino)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[2-(methylsulfanyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[2-(phenylamino)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[2-(phenylcarbonyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[2-(phenylsulfanyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[2-(propan-2-yl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[2-(trifluoromethyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[3-(trifluoromethyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-8-[[4-(trifluoromethyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-methyl-N-phenyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-phenyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
1-[2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-1H-indole-3-carboxylic acid
-
2'-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5'-methyl-8'-(propan-2-yl)-5',8'-dihydro-6'H-spiro[cyclobutane-1,7'-pteridin]-6'-one
-
2-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1-(2,2,2-trifluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one
-
2-cyano-3-hydroxy-3-methyl-N-[4-(trifluoromethoxy)phenyl]-propenamide
LFM-A12
2-[(3-cyano-6-methoxyquinolin-2-yl)sulfanyl]-N-(2-methoxy-5-methylphenyl)acetamide
i.e. I2
2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5,7,7-trimethyl-8-(propan-2-yl)-7,8-dihydropteridin-6(5H)-one
-
2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-7-(2,2,2-trifluoroethyl)-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridin-6(5H)-one
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxy-1H-benzimidazol-1-yl)thiophene-2-carboxamide
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-methoxy-1H-benzimidazol-1-yl)thiophene-2-carboxamide
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-[[(2R)-2,3-dihydroxypropyl]oxy]-1H-benzimidazol-1-yl)thiophene-2-carboxamide
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-[[(2R)-2-hydroxy-3-pyrrolidin-1-ylpropyl]oxy]-1H-benzimidazol-1-yl)thiophene-2-carboxamide
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-[[(4R)-1-methylazepan-4-yl]oxy]-1H-benzimidazol-1-yl)thiophene-2-carboxamide
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-[[(4S)-1-methylazepan-4-yl]oxy]-1H-benzimidazol-1-yl)thiophene-2-carboxamide
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[6-[(1-methylpiperidin-4-yl)methoxy]-1H-benzimidazol-1-yl]thiophene-2-carboxamide
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[6-[(1-methylpiperidin-4-yl)oxy]-1H-benzimidazol-1-yl]thiophene-2-carboxamide
-
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[6-[3-(dimethylamino)propoxy]-1H-benzimidazol-1-yl]thiophene-2-carboxamide
-
3-[(1S)-1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxy-1H-benzimidazol-1-yl)thiophene-2-carboxamide
-
3-[(2-chlorobenzyl)oxy]-5-(5,6-dimethoxy-1H-benzimidazol-1-yl)thiophene-2-carboxamide
-
3-[1-[2-hydroxy-3-(pyrrolidin-1-yl)propyl]-1H-indol-3-yl]propanoic acid
-
4-((R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-pteridin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide
BI 2536
4-[7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-6-oxo-6,7-dihydropteridin-8(5H)-yl]benzonitrile
-
5-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrrole-3-carboxamide
-
5-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1-[2-(tetrahydro-2H-pyran-4-yloxy)ethyl]-1H-pyrrole-3-carboxamide
-
5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-[[2-(trifluoromethyl)benzyl]oxy]thiophene-2-carboxamide
-
5-(6-methoxy-1H-benzimidazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
-
5-[6-(piperidin-4-yloxy)-1H-benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
-
5-[6-[(1-methylpiperidin-4-yl)methoxy]-1H-benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
-
5-[6-[(1-methylpiperidin-4-yl)oxy]-1H-benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
-
7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5,7-dimethyl-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridin-6(5H)-one
-
7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1H-pyrazol-3-yl)-7,8-dihydropteridin-6(5H)-one
-
7-ethyl-5-methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
-
7-ethyl-5-methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-[5-(pyridin-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
-
7-ethyl-5-methyl-8-phenyl-2-(2-phenyl-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-one
-
7-ethyl-8-(4-fluorophenyl)-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-7,8-dihydropteridin-6(5H)-one
-
8-(3,3-difluorocyclopentyl)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-7,8-dihydropteridin-6(5H)-one
-
8-(biphenyl-2-ylamino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-(phenylamino)-1-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-(phenylamino)-1-(propan-2-yl)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-(phenylamino)-1-[2-(piperidin-1-yl)ethyl]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(2-acetylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(2-aminophenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(2-benzylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(2-carbamoylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(2-fluorophenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(2-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(3-acetylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(3-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(4-acetylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[(4-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[[2-(acetylamino)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[[2-acetyl-3-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[[2-acetyl-4-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[[2-acetyl-5-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
8-[[2-methoxy-5-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
CHIR-258
selectivity profile of PLK2/4 over PLK1/3
cyclic [-CH2-CO-N[2-(1H-indol-3-yl)ethyl]-CH2-CO-Leu-His-Ser-pThr-NH-CH[CONH2]-CH2-S-]
-
cyclic [-CH2-CO-N[3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-CH2-CO-Leu-His-Ser-p-Thr-NH-CH[CONH2]-CH2-S-]
-
cyclic [-CH2-CO-N[6-[[2-(1-acetyl-1H-indol-3-yl)ethyl]amino]-6-oxohexyl]-CH2-CO-Leu-His-Ser-pThr-NH-CH[CONH2]-CH2-S-]
-
cyclic [-CH2-CO-N[6-[[2-(1-acetyl-1H-indol-3-yl)ethyl]amino]-6-oxohexyl]-CH2-CO-Leu-His[N3-(8-phenyloctyl)]-Ser-pThr-NH-CH[CONH2]-CH2-S-]
-
ethyl 1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate
-
GO 6976
loses PLK1 activity by at least an order of magnitude, relative to staurosporine
methyl 2-[(3-carbamoyl-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl)amino]benzoate
-
N,1-dimethyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-chlorobenzylaniline
-
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-methoxybenzylaniline
-
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-methylbenzylaniline
-
N-(2-(3-(1H-indol-1-yl)propoxy)phenyl)-4-methoxybenzamide
a highly selective inhibitor of Plk1, in vitro kinase inhibitory profile of 5i, overview
N-cyclopentyl-1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
N-cyclopropyl-1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
-
N-[4-[(6-chloropyridin-3-yl)methoxy]-3-methoxybenzyl]-2-(3,4-dimethoxyphenyl)ethanamine
SBE13
ONO1910
inhibits Plk1 activity without significantly impacting Plk3 activity in vitro
RNA
RNA interference abrogates centrosome maturation, spindle bipolarization, and silencing of the spindle assembly checkpoint
RNAi
down-regulation of Plk1 protein level by ca. 90%, abolishes the mobility-shifted, hyperphosphorylated form of BubR1 in the prometaphase-arrested cells
-
tert-butyl 1-methyl-2-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-4-oxo-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate
-
Wortmannin
time-dependent irreversible inhibition with PLK1
[1-[2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-1H-indol-3-yl]acetic acid
a highly selective inhibitor of Plk1, poor inhibition of Plk2 and Plk3
(4E)-4-(hydroxyimino)-5-methyl-2-(propan-2-yl)cyclohexa-2,5-dien-1-one
i.e. poloxime, PXE
(4E)-5-methyl-4-{[(2-methylbenzoyl)oxy]imino}-2-(propan-2-yl)cyclohexa-2,5-dien-1-one
-
(4E)-5-methyl-4-{[(2-methylbenzoyl)oxy]imino}-2-(propan-2-yl)cyclohexa-2,5-dien-1-one
i.e. poloxin
BI 2536
remarkable potency and selectivity towards Plk1, HeLa cells treated with BI 2536 are first delayed in prophase, after reluctantly entering mitosis, cells become blocked in prometaphase with aberrant monopolar spindles that fail to attach stably to chromosomes
BI-2536
blocks contractile ring assembly by preventing the localization of Rho and Rho-GEF without affecting the assembly of the central spindle
BI-2536
potential anti-cancer therapeutic agent, shows strong selectivity for Plk1
BTO-1
blocks contractile ring assembly by preventing the localization of Rho and Rho-GEF without affecting the assembly of the central spindle
N-[2-methoxy-5-({[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl}methyl)phenyl]glycine
-
N-[2-methoxy-5-({[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl}methyl)phenyl]glycine
i.e. ON01910, exhibits little activity against Plk1 in vitro, effective in inhibiting the cell proliferation
siRNA
depletion of Plk1, which leads to loss of BubR1 hyperphosphorylation, but has no significant effects on BubR1 localization
-
siRNA
reduces serine phosphorylation of HsCdc14A but not HsCdc14 protein level
-
additional information
the kinase activity is regulated by the conserved C-terminal polo box domain which acts as both an autoinhibitory domain and a subcellular localization domain
-
additional information
-
the kinase activity is regulated by the conserved C-terminal polo box domain which acts as both an autoinhibitory domain and a subcellular localization domain
-
additional information
1-NM-PP1 and 3-MB-PP1 have little effect on wild-type
-
additional information
-
1-NM-PP1 and 3-MB-PP1 have little effect on wild-type
-
additional information
design and synthesis of series of small-molecule non-ATP-competitive Plk1 inhibitors targeting the substrate-binding pocket are designed through rational drug design, molecular docking. Some comound are selective against inhibitory selectivity against polo kinases Plk2 and Plk3. Growth inhibition activity with HeLa and MCF-7 cells
-
additional information
identification of indole-3-carboxylic acids as non-ATP-competitive Plk1 inhibitors
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00126
(7R)-2-[5-(2,4-difluorophenyl)-1H-pyrazol-4-yl]-7-ethyl-5-methyl-8-(1-methyl-1H-pyrazol-4-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00135
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1-methyl-1H-pyrazol-3-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00327
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1-methyl-1H-pyrazol-4-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.0288
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1-methyl-1H-pyrazol-5-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00867
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1H-pyrazol-4-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00355
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00753
(7R)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-[(3S)-tetrahydrofuran-3-yl]-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00025
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00087
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-(propan-2-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00776
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-(pyrimidin-5-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00048
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-[(3R)-tetrahydrofuran-3-yl]-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00038
(7R)-7-ethyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-8-[(3S)-tetrahydrofuran-3-yl]-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00303
(7R)-7-ethyl-5-methyl-8-(1H-pyrazol-4-yl)-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00025
(7R)-7-ethyl-5-methyl-8-(tetrahydro-2H-pyran-4-yl)-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00141
(7R)-7-ethyl-5-methyl-8-(tetrahydrofuran-3-yl)-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00939
(7R)-8-(3,3-difluorocyclobutyl)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.01
1-(1-methylpiperidin-4-yl)-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
larger than 0.010, pH 7.9, 25°C
0.000102
1-(2-hydroxyethyl)-2-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one
Homo sapiens
pH and temperature not specified in the publication
0.000151
1-(2-hydroxyethyl)-5-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1H-pyrrole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.009
1-acetyl-L-prolyl-L-leucyl-3-(5-[[(Z)-benzylideneamino]oxy]pentyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.00505
1-acetyl-L-prolyl-L-leucyl-3-(6-[[(Z)-benzylideneamino]oxy]hexyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.000121
1-acetyl-L-prolyl-L-leucyl-3-(8-phenyloctyl)-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.00155
1-acetyl-L-prolyl-L-leucyl-3-[5-([(Z)-[(2-fluoro-6-phenoxyphenyl)methylidene]amino]oxy)pentyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.000139
1-acetyl-L-prolyl-L-leucyl-3-[6-(2-phenoxyphenyl)hexyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.00067
1-acetyl-L-prolyl-L-leucyl-3-[6-([(Z)-[(2-fluoro-6-phenoxyphenyl)methylidene]amino]oxy)hexyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.000066
1-acetyl-L-prolyl-L-leucyl-3-[8-(2-fluoro-6-phenoxyphenyl)octyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.000052
1-acetyl-L-prolyl-L-leucyl-3-[8-(2-phenoxyphenyl)octyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.000043
1-acetyl-L-prolyl-L-leucyl-3-[8-([1,1'-biphenyl]-2-yl)octyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.000032
1-acetyl-L-prolyl-L-leucyl-3-[8-[2-(benzyloxy)phenyl]octyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.000139
1-acetyl-L-prolyl-L-leucyl-3-[9-(2-fluoro-6-phenoxyphenyl)nonyl]-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
at pH 7.4 and 25°C
0.3
1-acetyl-L-prolyl-L-leucyl-L-histidyl-L-seryl-O-phosphono-L-threoninamide
Homo sapiens
IC50 above 0.3 mM, at pH 7.4 and 25°C
0.000143
1-cyclohexyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000009
1-methyl-2-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one
Homo sapiens
pH and temperature not specified in the publication
0.000015
1-methyl-5-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1H-pyrrole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000018
1-methyl-5-(2-[[5-(piperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1H-pyrrole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000068
1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.00011
1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid
Homo sapiens
pH 7.9, 25°C
0.000015
1-methyl-8-[(2-methylphenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000488
1-methyl-8-[(2-nitrophenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000278
1-methyl-8-[(2-phenoxyphenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.003733
1-methyl-8-[(2-sulfamoylphenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.01
1-methyl-8-[(3-nitrophenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
larger than 0.010, pH 7.9, 25°C
0.01
1-methyl-8-[(4-nitrophenyl)amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
larger than 0.010, pH 7.9, 25°C
0.00011
1-methyl-8-[[2-(methylamino)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000097
1-methyl-8-[[2-(methylsulfanyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000949
1-methyl-8-[[2-(phenylamino)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.001969
1-methyl-8-[[2-(phenylcarbonyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.002033
1-methyl-8-[[2-(phenylsulfanyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000365
1-methyl-8-[[2-(propan-2-yl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000432
1-methyl-8-[[2-(trifluoromethyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000051
1-methyl-8-[[3-(trifluoromethyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000872
1-methyl-8-[[4-(trifluoromethyl)phenyl]amino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.01
1-methyl-N-phenyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
larger than 0.010, pH 7.9, 25°C
0.01
1-phenyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
larger than 0.010, pH 7.9, 25°C
0.00347
1-[2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-1H-indole-3-carboxylic acid
Homo sapiens
pH 7.5, 30°C
0.0021
1-[2-hydroxy-3-(piperidin-1-yl)propyl]-1H-indole-3-carboxylic acid
Homo sapiens
pH 7.5, 30°C
0.00484
1-[2-hydroxy-3-(pyrrolidin-1-yl)propyl]-1H-indole-3-carboxylic acid
Homo sapiens
pH 7.5, 30°C
0.00191
1-[3-(diethylamino)-2-hydroxypropyl]-1H-indole-3-carboxylic acid
Homo sapiens
pH 7.5, 30°C
0.0253
2'-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5'-methyl-8'-(propan-2-yl)-5',8'-dihydro-6'H-spiro[cyclobutane-1,7'-pteridin]-6'-one
Homo sapiens
22°C, pH not specified in the publication
0.000028
2-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1-(2,2,2-trifluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one
Homo sapiens
pH and temperature not specified in the publication
0.00218
2-methyl-5-(propan-2-yl)cyclohexa-2,5-diene-1,4-dione
Homo sapiens
pH 7.5, 30°C
0.00348
2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-7-(2,2,2-trifluoroethyl)-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.0000008
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxy-1H-benzimidazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
0.000001
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-methoxy-1H-benzimidazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
0.000001
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-[[(2R)-2,3-dihydroxypropyl]oxy]-1H-benzimidazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
0.000003
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-[[(2R)-2-hydroxy-3-pyrrolidin-1-ylpropyl]oxy]-1H-benzimidazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
0.000004
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-[[(4R)-1-methylazepan-4-yl]oxy]-1H-benzimidazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
0.000003
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-(6-[[(4S)-1-methylazepan-4-yl]oxy]-1H-benzimidazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
0.000006
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[6-[(1-methylpiperidin-4-yl)methoxy]-1H-benzimidazol-1-yl]thiophene-2-carboxamide
Homo sapiens
-
0.000002
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[6-[(1-methylpiperidin-4-yl)oxy]-1H-benzimidazol-1-yl]thiophene-2-carboxamide
Homo sapiens
-
0.000004
3-[(1R)-1-(2-chlorophenyl)ethoxy]-5-[6-[3-(dimethylamino)propoxy]-1H-benzimidazol-1-yl]thiophene-2-carboxamide
Homo sapiens
-
0.00003
3-[(1S)-1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxy-1H-benzimidazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
0.000002
3-[(2-chlorobenzyl)oxy]-5-(5,6-dimethoxy-1H-benzimidazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
0.00571
3-[1-[2-hydroxy-3-(piperidin-1-yl)propyl]-1H-indol-3-yl]propanoic acid
Homo sapiens
pH 7.5, 30°C
0.0029
3-[1-[2-hydroxy-3-(pyrrolidin-1-yl)propyl]-1H-indol-3-yl]propanoic acid
Homo sapiens
pH 7.5, 30°C
0.00000083
4-((R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-pteridin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide
Homo sapiens
-
0.00376
4-[7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-6-oxo-6,7-dihydropteridin-8(5H)-yl]benzonitrile
Homo sapiens
22°C, pH not specified in the publication
0.0000018
5-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrrole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000272
5-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-1-[2-(tetrahydro-2H-pyran-4-yloxy)ethyl]-1H-pyrrole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000002
5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-[[2-(trifluoromethyl)benzyl]oxy]thiophene-2-carboxamide
Homo sapiens
-
0.000003
5-(6-methoxy-1H-benzimidazol-1-yl)-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
Homo sapiens
-
0.000003
5-[6-(piperidin-4-yloxy)-1H-benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
Homo sapiens
-
0.000007
5-[6-[(1-methylpiperidin-4-yl)methoxy]-1H-benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
Homo sapiens
-
0.000002
5-[6-[(1-methylpiperidin-4-yl)oxy]-1H-benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
Homo sapiens
-
0.00716
7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5,7-dimethyl-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00342
7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-8-(1H-pyrazol-3-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00182
7-ethyl-5-methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00182
7-ethyl-5-methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-[5-(pyridin-2-yl)-1H-pyrazol-4-yl]-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00283
7-ethyl-5-methyl-8-phenyl-2-(2-phenyl-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00234
7-ethyl-8-(4-fluorophenyl)-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.00032
8-(3,3-difluorocyclopentyl)-7-ethyl-2-[2-(4-fluorophenyl)-1H-imidazol-1-yl]-5-methyl-7,8-dihydropteridin-6(5H)-one
Homo sapiens
22°C, pH not specified in the publication
0.001565
8-(biphenyl-2-ylamino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000006
8-(phenylamino)-1-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.00043
8-(phenylamino)-1-(propan-2-yl)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.01
8-(phenylamino)-1-[2-(piperidin-1-yl)ethyl]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
larger than 0.010, pH 7.9, 25°C
0.000248
8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000346
8-[(2-acetylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.00015
8-[(2-aminophenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000943
8-[(2-benzylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.002076
8-[(2-carbamoylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000125
8-[(2-fluorophenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000042
8-[(2-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.0001
8-[(3-acetylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000135
8-[(3-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000197
8-[(4-acetylphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000256
8-[(4-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.002523
8-[[2-(acetylamino)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.002051
8-[[2-acetyl-3-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000464
8-[[2-acetyl-4-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000109
8-[[2-acetyl-5-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.00004
8-[[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.000007
8-[[2-methoxy-5-(4-methylpiperazin-1-yl)phenyl]amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.0098
cyclic (-CH2-CO-Pro-Leu-His-Ser-pThr-Cys-S-)
Homo sapiens
25°C, pH not specified in the publication
0.0085
cyclic [-CH2-CO-N[2-(1H-indol-3-yl)ethyl]-CH2-CO-Leu-His-Ser-pThr-NH-CH[CONH2]-CH2-S-]
Homo sapiens
25°C, pH not specified in the publication
0.0048
cyclic [-CH2-CO-N[3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-CH2-CO-Leu-His-Ser-p-Thr-NH-CH[CONH2]-CH2-S-]
Homo sapiens
25°C, pH not specified in the publication
0.0026
cyclic [-CH2-CO-N[6-[[2-(1-acetyl-1H-indol-3-yl)ethyl]amino]-6-oxohexyl]-CH2-CO-Leu-His-Ser-pThr-NH-CH[CONH2]-CH2-S-]
Homo sapiens
25°C, pH not specified in the publication
0.0011
cyclic [-CH2-CO-N[6-[[2-(1-acetyl-1H-indol-3-yl)ethyl]amino]-6-oxohexyl]-CH2-CO-Leu-His[N3-(8-phenyloctyl)]-Ser-pThr-NH-CH[CONH2]-CH2-S-]
Homo sapiens
25°C, pH not specified in the publication
0.01
ethyl 1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate
Homo sapiens
larger than 0.010, pH7.9, 25°C
0.001117
methyl 2-[(3-carbamoyl-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazolin-8-yl)amino]benzoate
Homo sapiens
pH 7.9, 25°C
0.004215
N,1-dimethyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
pH 7.9, 25°C
0.0026
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-2-methylbenzamide
Homo sapiens
pH 7.5, 30°C
0.01
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-2-nitrobenzamide
Homo sapiens
pH 7.5, 30°C
0.00322
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-chlorobenzylaniline
Homo sapiens
pH 7.5, 30°C
0.00093
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-methoxybenzamide
Homo sapiens
pH 7.5, 30°C
0.00205
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-methoxybenzylaniline
Homo sapiens
pH 7.5, 30°C
0.00709
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-methylbenzamide
Homo sapiens
pH 7.5, 30°C
0.00466
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-methylbenzylaniline
Homo sapiens
pH 7.5, 30°C
0.01
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-nitrobenzamide
Homo sapiens
pH 7.5, 30°C
0.01
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-4-nitrobenzylaniline
Homo sapiens
pH 7.5, 30°C
0.00683
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-acetamide
Homo sapiens
pH 7.5, 30°C
0.00633
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-benzamide
Homo sapiens
pH 7.5, 30°C
0.00948
N-(2-(3-(1H-benzo[d]imidazol-1-yl)propoxy)phenyl)-benzylaniline
Homo sapiens
pH 7.5, 30°C
0.00559
N-(2-(3-(1H-indol-1-yl)propoxy)phenyl)-2-methylbenzamide
Homo sapiens
pH 7.5, 30°C
0.01
N-(2-(3-(1H-indol-1-yl)propoxy)phenyl)-2-nitrobenzamide
Homo sapiens
pH 7.5, 30°C
0.00068
N-(2-(3-(1H-indol-1-yl)propoxy)phenyl)-4-methoxybenzamide
Homo sapiens
pH 7.5, 30°C
0.01
N-(2-(3-(1H-indol-1-yl)propoxy)phenyl)-4-nitrobenzamide
Homo sapiens
pH 7.5, 30°C
0.01
N-cyclopentyl-1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
larger than 0.010, pH 7.9, 25°C
0.01
N-cyclopropyl-1-methyl-8-(phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
Homo sapiens
larger than 0.010, pH 7.9, 25°C
0.0000002
N-[4-[(6-chloropyridin-3-yl)methoxy]-3-methoxybenzyl]-2-(3,4-dimethoxyphenyl)ethanamine
Homo sapiens
-
0.000817
tert-butyl 1-methyl-2-(2-[[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino]pyrimidin-4-yl)-4-oxo-1,4,6,7-tetrahydro-5H-pyrrolo[3,2-c]pyridine-5-carboxylate
Homo sapiens
pH and temperature not specified in the publication
0.00188
[1-[2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-1H-indol-3-yl]acetic acid
Homo sapiens
pH 7.5, 30°C
0.00096
[1-[2-hydroxy-3-(morpholin-4-yl)propyl]-1H-indol-3-yl]acetic acid
Homo sapiens
pH 7.5, 30°C
0.00041
[1-[2-hydroxy-3-(piperidin-1-yl)propyl]-1H-indol-3-yl]acetic acid
Homo sapiens
pH 7.5, 30°C
0.00013
[1-[2-hydroxy-3-(pyrrolidin-1-yl)propyl]-1H-indol-3-yl]acetic acid
Homo sapiens
pH 7.5, 30°C
0.00264
[1-[3-(diethylamino)-2-hydroxypropyl]-1H-indol-3-yl]acetic acid
Homo sapiens
pH 7.5, 30°C
additional information
additional information
Homo sapiens
IC50 values for cell growth inhibition of HeLa and MCF-7 cells
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
491394, 491395, 491396, 491397, 661586, 662420, 663203, 677343, 678284, 678324, 679094, 679095, 679108, 679362, 680011, 680773, 680810, 682486, 682562, 682567, 693194, 694505, 702558, 702943, 703011, 703018, 703030, 703103, 703224, 704076, 704521, 705070, 705078, 705692, 705801, 706460, 706517, 726683, 727147, 727149, 727163, 727936, 728024, 739963, 740124, 740152, 741007, 760695, 760764, 760980, 762085
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Plk1 abundance and kinase activity are strongly upregulated at the G2/M transition, reach a peak during mitosis, and are downregulated by the subsequent G1 phase, albeit with slower kinetics than Cdk1/cyclin B activity, which falls acutely at anaphase onset
primary, when activated by phytohemagglutinin, a high level of PLK transcripts results within 2-3 days. In some cases, addition of interleukin 2 to these cells increases the expression of PLK mRNA further
additional information
increased requirement for Plk1 in comparison to normal cells
screening of a lambdagt 10 library, full-length construct
additional information
no PLK transcripts are found in normal adult lung, brain, heart, liver, kidney, skeletal muscle, and pancreas, resting peripheral lymphocytes do not express the gene at all. Primary cultures of human peripheral macrophages, which are not dividing under the culture conditions applied, showed very little or no PLK mRN
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
at anaphase onset, Plk1 redistributes onto equatorial microtubule bundles that define the spindle midzone or central spindle, and remain tightly associated with these microtubules during midbody formation and completion of cytokinesis
additional information
after transfection into PC3 cells, HeLa cells and NIH 3T3 cells, Plk1 localization is controlled not only by the polo box domain, the kinase domain is also involved in Plk1 targeting mechanism to the centrosome
co-distributes with HsCdc14A to the centrosomes from prophase to metaphase
BubR1 colocalizes with Plk1 at kinetochores of unaligned chromosomes
kinetochore localization of BubR1 and Plk1 is important for BubR1 hyperphosphorylation
rapidly accumulates at kinetochores, appears to be partially released once all chromosomes are properly congressed at the metaphase plate
the enzyme localizes to prometaphase kinetochores and is reduced at metaphase kinetochores
by anaphase, PLK1 relocates from the centrosome to the central spindle while HsCdc14A is still at centrosome
Plk1 is expressed during G2 and mitosis at the spindle pole and spindle midzone
additional information
the kinase activity is regulated by the conserved C-terminal polo box domain which acts as both an autoinhibitory domain and a subcellular localization domain
-
additional information
-
the kinase activity is regulated by the conserved C-terminal polo box domain which acts as both an autoinhibitory domain and a subcellular localization domain
-
additional information
-
at telophase, PLK1 localization is only at the mid-body where HsCdc14A is also apparent
-
additional information
at telophase, PLK1 localization is only at the mid-body where HsCdc14A is also apparent
-
additional information
Plk1 is expressed during G2 and mitosis at the midbody
-
additional information
Plk1 is expressed during G2 and mitosis at the midbody
-
additional information
Plk1 is expressed during G2 and mitosis at the midbody
-
additional information
-
translocates to the midbody during telophase, RhoA is also enriched at the midbody region during telophase and colocalizes with Plk1
-
additional information
translocates to the midbody during telophase, RhoA is also enriched at the midbody region during telophase and colocalizes with Plk1
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the serine/threonine kinase Polo-like kinase 1 (Plk1) is a member of the Polo-like kinases family
malfunction
physiological function
malfunction
combination treatment with PLK1 and Bcl2 pharmacological inhibitors specifically induces synergistic cell death, partly because of PLK1 inhibitor-mediated depletion of Myc and Mcl1 expression
malfunction
upon PLK1 inhibition, phosphorylated histone H3 on Thr 3, a marker of Haspin activity, is reduced. PLK1 inhibition, together with partial inhibition of Aurora B, allows efficient spindle assembly checkpoint override to occur. This phenotype is more pronounced than the phenotype observed by combining the same PLK1 inhibitors with partial MPS1 inhibition. PLK1 inhibition does not obviously cooperate with Haspin inhibition to promote spindle assembly checkpoint override. Effects of the PLK1 inhibitors together with partial inhibition of the three major checkpoint kinases Aurora B, MPS1 and Haspin in maintaining the strength of the nocodazole induced mitotic arrest, overview
malfunction
complete inhibition of polo kinase 1 can prevent mitotic entry for hours in a vast majority of TERT-RPE1, HeLa or RKO cells, even without prior activation of the DNA damage checkpoint
malfunction
enzyme downregulation in metastatic prostate cancer cells enhances epithelial characteristics and inhibits cell motility
physiological function
conserved function in mitotic processes and cytokinesis
physiological function
Plk1 function as a key regulator of mitotic events by phosphorylating substrate proteins of centrosomes, kinetochores, the mitotic spindle, and the midbody
physiological function
Plk1 is a critical regulator of many stages of mitosis
physiological function
Plk1 is a fundamental regulator of mitotic progression
physiological function
PLK1 is a key regulator of multiple steps during mitotic progression
physiological function
PLK1 is the upstream regulator of SYK tyrosine kinase in B-lineage acute lymphoblastic leukemia cells
physiological function
PLK1 plays a critical role in regulating the cell cycle, PLK inhibition increases gene expression of paramyxovirus
physiological function
PLK1 represents the most studied member of this familiy and has known roles throughout mitosis, including mitotic entry, spindle formation, chromosome segregation, and cytokinesis
physiological function
the dynamics of the enzyme at kinetochores control two critical mitotic processes: initially establishing correct kinetochore-microtubule attachments and subsequently silencing the spindle checkpoint
physiological function
the enzyme has multiple functions and substrates in mitosis
physiological function
enzyme Plk1 acts as a regulator in multiple stages of mitotic progression
physiological function
PLK1 promotes Fbw7 phosphorylation, selfubiquitination, and proteasomal degradation, creating a PLK1-Myc feedforward activation loop in MYC overexpressing tumor cells. PLK1 specifically binds to the SCFFbw7 ubiquitin ligase, phosphorylates it, and promotes its autopolyubiquitination and proteasomal degradation, counteracting Fbw7-mediated degradation of N-Myc and additional substrates, including cyclin E and Mcl1. Stabilized N-Myc in turn directly activates PLK1 transcription, constituting a positive feedforward regulatory loop that reinforces Myc-regulated oncogenic programs, association between Myc deregulation and PLK1 dependence. Analysis of the molecular mechanism responsible for reciprocal activation between Polo-like kinase-1 and N-Myc, PLK1-Fbw7-Myc signaling circuit, overview. PLK1 Reduces Fbw7 stability through promotion of its phosphorylation and autopolyubiquitination, Fbw7 turnover is mediated by autocatalytic ubiquitin transfer
physiological function
Polo-like kinase 1 (PLK1) plays many roles leading to cell division including promoting entry into, progression through and exit from mitosis. It regulates bipolar spindle formation, centrosome function and k-MT attachment in human cells. PLK1 kinase activity is required in the maintenance of a robust spindle assembly checkpoint. PLK1 kinase plays a major role in mitosis. In nocodazole-arrested U2OS cells, PLK1 activity is continuously required for maintaining Aurora B protein localisation and activity at kinetochores (Aurora B is required for the recruitment of outer kinetochore proteins). Aurora B inhibition causes PLK1 to relocalise from kinetochores into fewer and much larger foci, possibly due to incomplete recruitment of outer kinetochore proteins. PLK1 is directly involved in maintaining efficient spindle assembly checkpoint signalling, possibly by cooperating in a positive feedback loop with Aurora B, and that partially redundant mechanisms exist which reinforce the spindle assembly checkpoint. PLK1 activity appears to be required for continuous maintenance of levels of histone H3 phosphorylated at Thr3 and its accumulation at kinetochores. Upon disruption of microtubules in U2-OS cells PLK1 functions to cooperate with Aurora B to maintain a mitotic cell cycle arrest
physiological function
polo kinase 1 is essential for mitotic entry in human cells
physiological function
the enzyme is a key regulator of epithelial-to-mesenchymal transition and cell motility in normal prostate epithelium and prostate cancer. The enzyme is a potent activator of MAPK signaling
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PLK1_HUMAN
603
0
68255
Swiss-Prot
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
the enzyme is activated by phosphorylation of Thr210 by protein phosphatase 1
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of the PBD in complex with nonphysiological and control target peptides Cdc25C and Cdc25C-P, to 1.95 A, 2.10 A, and 2.80 A resolution, Trp-414 is fundamental in substrate recognition regardless of its phosphorylation status
Plk1 polo-box domain in complex with unphosphorylated and phosphorylated Cdc25C, to 2.1 and 2.85 A resolution, respectively, by the sitting-drop method, crystals of the polo-box domain in complex with the phosphorylated peptide belong to the orthorhombic space group P212121, with unit-cell parameters a = 38.23, b = 67.35, c = 88.25 A, alpha = gamma = beta = 90°, and contain one molecule per asymmetric unit. Crystals of the polo-box domain in complex with the unphosphorylated peptide belong to the monoclinic space group P21, with unit-cell parameters a = 40.18, b = 49.17, c = 56.23 A, alpha = gamma = 90°, beta = 109.48°, and contain one molecule per asymmetric unit
purified untagged recombinant selenomethionine-labeled enzyme comprising residues 367-603, cleavage through subtilisin, sitting drop vapour diffusion method, 4°C, 0.001 ml of protein solution containing 10 mg/ml protein is mixed with 0.001 ml mother liquor containing 5-10% v/v PEG 4000, 0.1 M sodium citrate, pH 6.0, and 0.1 M ammonium acetate, formation of needle-like crystals that do not diffract, co-crystallization with the synthesized phosphopeptide MQSpTPL is suitable for crystallization giving crystals within 2-3 days by sitting drop vapour diffusion from 1-10% PEG 20000, 0.1 M MES, pH 6.5, at room temperature, X-ray diffraction structure determination and analysis at 2.2-2.3 A resolution, complex formation between enzyme and phosphopeptide via residues W414, L490, H538, and K540
wild-type, to ca. 3 A resolution, T210V mutant complexed with the nonhydrolyzable ATP analogue AMP-PNP or the pyrrolo-pyrazole inhibitor PHA-680626 at 2.4 and 2.1 A resolution, respectively, by the hanging drop method, typical kinase fold with the unphosphorylated (mutant T210V) activation loop in an extended conformation, stabilized by a crystal contact, presence of a phenylalanine at the bottom of the ATP pocket, combined with a cysteine in the roof of the binding site, a pocket created by Leu132 in the hinge region, and a cluster of positively charged residues in the solvent-exposed area outside of the adenine pocket adjacent to the hinge region
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C67V/L130G
localizes to centrosomes and kinetochores in mitotic cells like the wild-type, is ca. 12fold less active than wild-type in the presence of ATP, both 1-NM-PP1 and 3-MB-PP1 inhibit rapidly, selectively, and reversibly its growth in a dose-dependent manner. Acute treatment during anaphase prevents recruitment of both Plk1 itself and the Rho guanine nucleotide exchange factor Ect2 to the central spindle, abolishes RhoA GTPase localization to the equatorial cortex, and suppresses cleavage furrow formation and cell division. 3-MB-PP1 elicits a more penetrant phenotype that is virtually identical to PLK1 deletion
EGFP-Plk1D176N
construct used in FRAP experiments, expressed in U2OS cells, kinase-dead mutant
EGFP-Plk1PBD
construct used in FRAP experiments, expressed in U2OS cells, only C-terminal PBD domain
EGFP-Plk1T210A
construct used in FRAP experiments, expressed in U2OS cells, nonphosphorylatable T-loop form of Plk1
EGFP-Plk1T210D
construct used in FRAP experiments, expressed in U2OS cells, constitutively active mutant
H538A/K540M
localizes at the centrosome, when wild-type Plk1 and H538A/K540M are fused to EGFP. After photobleaching recovers its signal at the centrosome following very similar kinetics as the wild-type
K82M
PLK1-PBD H538A/K540M
PLK1 polo box domain double mutant, constructed for the determination of the specificity of the association of PLK1 with MAVS
PLK1-PBD W414F/H538A/K540M
PLK1 polo box domain triple mutant, constructed for the determination of the specificity of the association of PLK1 with MAVS
T210D
T210V
W414F
abolishes molecular recognition and diminishes centrosomal localization
additional information
T210D
site-directed mutagenesis, hyperactive Plk1 mutant, shows reduced activity with truncated Pin1 compared to the wild-tpe Plk1
additional information
down-regulation of Plk1 by expression of hairpin shRNA results in increased Pin1 ubiquitination and to down-regulation of pin 1 levels during mitosis
additional information
-
down-regulation of Plk1 by expression of hairpin shRNA results in increased Pin1 ubiquitination and to down-regulation of pin 1 levels during mitosis
additional information
enzyme depletion using the vector-based small interfering RNA technique, Plk1 depletion leads to highly inhibited cell proliferation, decreased viability, and results in cell-cycle arrest with 4 n DNA content, formation of dumbbell-like chromatin structure due to impaired sister chromatin separation, induction of apoptosis, the apoptotic effect is reversible by co-transfection of murine Plk1
additional information
both copies of the PLK1 locus deleted in telomerase-immortalized human retinal pigment epithelial cells, more than 90% knockdown of Plk1 does not cause any cell cycle impairment, PLK1-null cells arrest in mitosis with immature centrosomes and monopolar spindles. Plk1 function and cell viability can be reconstituted by expressing either wildtype Plk1 or an analog-sensitive variant, the analog-sensitive variant is inhibited by 3-MB-PP1
additional information
-
both copies of the PLK1 locus deleted in telomerase-immortalized human retinal pigment epithelial cells, more than 90% knockdown of Plk1 does not cause any cell cycle impairment, PLK1-null cells arrest in mitosis with immature centrosomes and monopolar spindles. Plk1 function and cell viability can be reconstituted by expressing either wildtype Plk1 or an analog-sensitive variant, the analog-sensitive variant is inhibited by 3-MB-PP1
additional information
-
EGFP-Plk1 delta400-603 mutant, lacks the polo box domain, localizes to the centrosome and displays a similar fluorescence intensity to the W414F mutant
additional information
EGFP-Plk1 delta400-603 mutant, lacks the polo box domain, localizes to the centrosome and displays a similar fluorescence intensity to the W414F mutant
additional information
homozygous deletion of PLK1 fully abrogates its function in vivo, PLK1delta/delta cells have monopolar or disorganized bipolar spindles with adjacent and immature centrosomes
additional information
-
homozygous deletion of PLK1 fully abrogates its function in vivo, PLK1delta/delta cells have monopolar or disorganized bipolar spindles with adjacent and immature centrosomes
additional information
polo-box domain mutant in which residues His 538 and Lys 540, critical for ligand binding, are changed to alanine, do not pull down BubR1 from mitotic cell lysates
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by gel filtration
hexahistidine-tagged Plk1 is purified using HIS-select nickel affinity agarose
Plk1, aa 36-345, is expressed in H5 insect cells as GST fusion protein, the tag is removed and the ptotein is purified on an ion exchange column
purified Plk1 is obtained from HeLa cell extracts using a Q-Sepharose FF, a Heparin FF, a CM Sepharose FF, a poly(U) Sepharose 4B, and a substrate affinity column
recombinant selenomethionine-labeled GST-tagged Plk1 from Escherichia coli by glutathione affinity chromatography, the GST-tag is cleaved off, recombinant His-tagged Plk1 from Sf9 insect cells by nickel affinity chromatography
SYK and PLK1 immune complexes immunoprecipitated from whole cell lysates of NALM-6 and BT-20 cell lines
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
a full-length Myc-PLK1 plasmid is used, full-length PLK1, cloned into pDON207, is inserted into a pCINeo vector, pFLAG-PLK1-PBD and pEGFP-PLK1-PBD constructs are generated
expressed in Escherichia coli BL21(DE3) pLysS as a GST fusion protein, 293T cells co-transfected with FLAG-PLK1 and GFPHsCdc14A, GST-tagged PLK1 kinase expressed in insect, HeLa cells transiently transfected to express GFP-HsCdc14A and FLAG-PLK1
expression of GST-tagged Plk1 in Escherichia coli strain B834(DE3) strain as selenomethionine-labeled enzyme, expression of His-tagged Plk1 in Spodoptera frugiperda Sf9 cells using the baculovirus system
expression of Plk1 in HeLa cells, DU145 cells, T98G cells, and in GM05849 cells
into the vector pBluescript II KS+, subsequently into pET15b+ for expression in Escherichia coli BL21DE3 cells, and into pEGFP-C1
Plk1 cloned into vector pFastBac, the polo box domain cDNA sequence (residues 367-603) cloned into vector pGEX-6P-2. PC3 cells, HeLa cells and NIH 3T3 cells transfected with either EGFP-Plk1 or EGFP-Plk1 H538A/K540M
Plk1 polo-box domain cloned into vector pGEX-6P-2, overexpressed as a GST fusion protein in Escherichia coli BL21(DE3) plys strain
recombinant co-expression of Myc-tagged Fbw7 with PLK1 in HEK-293T cells, and expressed full-length PLK1 in combination with FLAG-tagged Fbw7 or truncation mutants
stable expression of Plk1 and transfection with hairpin shRNA in HeLa cells, expression of GST-tagged Plk1 in Spodoptera frugiperda Sf9 cells
the Plk1 3'-UTR region is amplified and cloned downstream of the luciferase gene into the pMIRREPORT luciferase vector
transduction of PLK1flox/delta cells with retroviruses expressing either wild-type Plk1 or the equivalent double mutant C67V/L130G, as EGFP fusions
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
inhibition of BCR/ABL by imatinib or nilotinib leads to decreased expression of PLK1 protein in CML cells
overexpression of Plk1 is commonly observed in many human malignancies, Plk expression is regulated by the microRNAs miR-100 and miR-142-5p
Plk is over-expressed in approximately 80% of human tumors of diverse origins
PLK1 is highly expressed in sarcoma cell lines and in osteosarcoma tissues
significantly over-expressed in basal cell carcinoma and squamous cell carcinoma
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
the development of an ELISA-based Plk1 assay is described that employs a principle to rapidly and accurately quantify the Plk1 activity with high sensitivity and specificity
drug development
medicine
pharmacology
combined inhibition of PLK1 and Bcl2 represent potential Myc-targeting therapeutics
additional information
drug development
roles of Plk1 in cell cycle progression and in mitosis, role for Plk1 in the activation of the CDK1-Cyclin B complex. Plk1 is required not only to obtain, but also to maintain, chromosome bi-orientation on the mitotic spindle, use of BI 2536, a small-molecule inhibitor of Plk1, as an analytical tool and potential cancer therapeutic
drug development
Plk1 is considered an attractive anti-cancer drug target due to its ability to promote tumorigenesis
medicine
correlation between Plk1 overexpression in tumors and poor patient prognosis, Plk1 acts at multiple discrete steps throughout late G2 phase, mitosis, and cytokinesis, triggers activation of the Ect2-RhoA network
medicine
in the study Plk1 is detected in 63.6% of Non-Hodgkin's Lymphoma cases and overexpression is positively linked to systemic symptom, elevated LDH level and higher IDI scores, Plk1 may be a new target in NHL therapy
medicine
it is possible that targeting PLK1 will enhance host innate immune responsees, leading to a novel strategy of clearing paramyxovirus infections quickly
medicine
knockdown of plk1 results in sensitization of multidrug resistant cells to doxorubicin, and this combination of gene silencing and small drug delivery may prove useful to achieve potent therapeutic effects
medicine
Plk1 attracts great attention in the field of cancer therapy because it exhibits generally elevated activity in cancer cells and is a negative prognostic factor for cancer patients
medicine
PLK1 can be a potential therapeutic target for the treatment of osteosarcoma
medicine
PLK1 is a promising target for the molecular therapy of anaplastic thyroid carcinoma, ATC
medicine
Plk1 is recognized as an attractive therapeutic target in the treatment of proliferative diseases
medicine
polo-like kinase may represent a novel drug target in imatinib-sensitive and imatinib-resistant chronic myeloid leukemia
medicine
polo-like kinases represent an attractive target for cancer treatment through interference with the cell cycle
medicine
targeting Plk1 will cause mitotic catastrophe, with significant cytotoxicity both in vitro and in vivo, underscoring the important therapeutic opportunity of Plk1 in nasopharyngeal cancer
medicine
the data demonstrate the function of Plk1 as a regulator of interferon induction and provide the basis for the development of inhibitors preventing the PLK1/MAVS association to sustain innate immunity
medicine
the skin is an attractive tissue for Plk1 based cancer chemoprevention and chemotherapeutic applications
additional information
late mitotic function of Plk1, kinase activity of Plk1 is needed for an early event in cytokinesis, acts upstream of RhoA, Plk1 activity is required for the equatorial localization of RhoA and its effectors during anaphase
additional information
-
late mitotic function of Plk1, kinase activity of Plk1 is needed for an early event in cytokinesis, acts upstream of RhoA, Plk1 activity is required for the equatorial localization of RhoA and its effectors during anaphase
additional information
-
Plk1 controls both spindle elongation and cytokinesis, coordinates chromosome segregation with cytokinesis through its dual control of anaphase B and contractile ring assembly
additional information
Plk1 controls both spindle elongation and cytokinesis, coordinates chromosome segregation with cytokinesis through its dual control of anaphase B and contractile ring assembly
additional information
Plk1 facilitates chromosome alignment during prometaphase through BubR1, Plk1 is necessary for not only proper spindle assembly but also the formation of functional kinetochore-microtubule attachments
additional information
Plk1 is responsible for causing mitotic BubR1 upshift, and attribute a kinetochore-specific function to the hyperphosphorylated form of BubR1 in the stabilization of kinetochore-microtubule interactions
additional information
-
RhoA and Plk1 physically interact, their interaction appears to be enhanced during mitosis, Plk1 may alter activation of RhoA during mitotic cytokinesis
additional information
RhoA and Plk1 physically interact, their interaction appears to be enhanced during mitosis, Plk1 may alter activation of RhoA during mitotic cytokinesis
additional information
-
temporal control of HsCdc14A phosphatase activity by PLK1 is essential for chromosome segregation in mitosis
additional information
temporal control of HsCdc14A phosphatase activity by PLK1 is essential for chromosome segregation in mitosis
additional information
with respect to both substrate and ATP-site specificity, highest similarity is between PLK2 and PLK3, PLK1 is next most similar, and PLK4 is least similar
additional information
with respect to both substrate and ATP-site specificity, highest similarity is between PLK2 and PLK3, PLK1 is next most similar, and PLK4 is least similar
additional information
with respect to both substrate and ATP-site specificity, highest similarity is between PLK2 and PLK3, PLK1 is next most similar, and PLK4 is least similar
additional information
with respect to both substrate and ATP-site specificity, highest similarity is between PLK2 and PLK3, PLK1 is next most similar, and PLK4 is least similar
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Holtrich, U.; Wolf, G.; Brauninger, A.; Karn, T.; Bohme, B.; Rubsamen-Waigmann, H.; Strebhardt, K.
Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors
Proc. Natl. Acad. Sci. USA
91
1736-1740
1994
Homo sapiens (P53350)
Hamanaka, R.; Maloid, S.; Smith, M.R.; O'Connell, C.D.; Longo, D.L.; Ferris, D.K.
Cloning and characterization of human and murine homologues of the Drosophila polo serine-threonine kinase
Cell Growth Differ.
5
249-257
1994
Homo sapiens (P53350), Homo sapiens, Mus musculus (Q07832), Mus musculus
Golsteyn, R.M.; Schultz, S.J.; Bartek, J.; Ziemiecki, A.; Ried, T.; Nigg, E.A.
Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5
J. Cell Sci.
107
1509-1517
1994
Homo sapiens (P53350)
-
Lake, R.J.; Jelinek, W.R.
Cell cycle- and terminal differentiation-associated regulation of the mouse mRNA encoding a conserved mitotic protein kinase
Mol. Cell. Biol.
13
7793-7801
1993
Homo sapiens (P53350), Mus musculus (Q07832)
Cheng, K.Y.; Lowe, E.D.; Sinclair, J.; Nigg, E.A.; Johnson, L.N.
The crystal structure of the human polo-like kinase-1 polo box domain and its phospho-peptide complex
EMBO J.
22
5757-5768
2003
Homo sapiens (P53350), Homo sapiens
Eckerdt, F.; Yuan, J.; Saxena, K.; Martin, B.; Kappel, S.; Lindenau, C.; Kramer, A.; Naumann, S.; Daum, S.; Fischer, G.; Dikic, I.; Kaufmann, M.; Strebhardt, K.
Polo-like kinase 1-mediated phosphorylation stabilizes Pin1 by inhibiting its ubiquitination in human cells
J. Biol. Chem.
280
36575-36583
2005
Homo sapiens (P53350), Homo sapiens
Liu, X.; Erikson, R.L.
Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells
Proc. Natl. Acad. Sci. USA
100
5789-5794
2003
Homo sapiens (P53350)
Garcia-Alvarez, B.; Ibanez, S.; Montoya, G.
Crystallization and preliminary X-ray diffraction studies on the human Plk1 Polo-box domain in complex with an unphosphorylated and a phosphorylated target peptide from Cdc25C
Acta Crystallogr. Sect. F
62
372-375
2006
Homo sapiens (P53350), Homo sapiens
Kothe, M.; Kohls, D.; Low, S.; Coli, R.; Cheng, A.C.; Jacques, S.L.; Johnson, T.L.; Lewis, C.; Loh, C.; Nonomiya, J.; Sheils, A.L.; Verdries, K.A.; Wynn, T.A.; Kuhn, C.; Ding, Y.H.
Structure of the catalytic domain of human polo-like kinase 1
Biochemistry
46
5960-5971
2007
Homo sapiens, Homo sapiens (P53350)
Johnson, E.F.; Stewart, K.D.; Woods, K.W.; Giranda, V.L.; Luo, Y.
Pharmacological and functional comparison of the polo-like kinase family: insight into inhibitor and substrate specificity
Biochemistry
46
9551-9563
2007
Homo sapiens (O00444), Homo sapiens (P53350), Homo sapiens (Q9H4B4), Homo sapiens (Q9NYY3)
Zimmerman, W.C.; Erikson, R.L.
Finding Plk3
Cell Cycle
6
1314-1318
2007
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens (P53350), Homo sapiens (Q9H4B4), Homo sapiens (Q9NYY3)
Randall, C.L.; Burkard, M.E.; Jallepalli, P.V.
Polo kinase and cytokinesis initiation in Mammalian cells: harnessing the awesome power of chemical genetics
Cell Cycle
6
1713-1717
2007
Homo sapiens (P53350), Homo sapiens
Dai, B.N.; Yang, Y.; Chau, Z.; Jhanwar-Uniyal, M.
Polo-like kinase 1 regulates RhoA during cytokinesis exit in human cells
Cell Prolif.
40
550-557
2007
Homo sapiens, Homo sapiens (P53350)
Plyte, S.; Musacchio, A.
PLK1 inhibitors: setting the mitotic death trap
Curr. Biol.
17
R280-R283
2007
Mus musculus, Homo sapiens (P53350), Homo sapiens
Elowe, S.; Huemmer, S.; Uldschmid, A.; Li, X.; Nigg, E.A.
Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of kinetochore microtubule interactions
Genes Dev.
21
2205-2219
2007
Homo sapiens (P53350)
Matsumura, S.; Toyoshima, F.; Nishida, E.
Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1
J. Biol. Chem.
282
15217-15227
2007
Mus musculus, Homo sapiens (P53350)
Yuan, K.; Hu, H.; Guo, Z.; Fu, G.; Shaw, A.P.; Hu, R.; Yao, X.
Phospho-regulation of HsCdc14A By Polo-like kinase 1 is essential for mitotic progression
J. Biol. Chem.
282
27414-27423
2007
Homo sapiens, Homo sapiens (P53350)
Brennan, I.M.; Peters, U.; Kapoor, T.M.; Straight, A.F.
Polo-like kinase controls vertebrate spindle elongation and cytokinesis
PLoS ONE
2
e409
2007
Homo sapiens, Homo sapiens (P53350)
Garcia-Alvarez, B.; de Carcer, G.; Ibanez, S.; Bragado-Nilsson, E.; Montoya, G.
Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization
Proc. Natl. Acad. Sci. USA
104
3107-3112
2007
Homo sapiens, Homo sapiens (P53350)
Burkard, M.E.; Randall, C.L.; Larochelle, S.; Zhang, C.; Shokat, K.M.; Fisher, R.P.; Jallepalli, P.V.
Chemical genetics reveals the requirement for Polo-like kinase 1 activity in positioning RhoA and triggering cytokinesis in human cells
Proc. Natl. Acad. Sci. USA
104
4383-4388
2007
Homo sapiens (P53350), Homo sapiens
Higashimoto, T.; Chan, N.; Lee, Y.K.; Zandi, E.
Regulation of IKK by phosphorylation of gamma binding domain of Ikappa Ba kinase beta by polo-like kinase 1
J. Biol. Chem.
283
35354-35367
2008
Homo sapiens (P53350)
Liu, L.; Zhang, M.; Zou, P.
Polo-like kinase 1 as a new target for non-Hodgkins lymphoma treatment
Oncology
74
96-103
2008
Homo sapiens (P53350)
Emmitte, K.A.; Adjabeng, G.M.; Adjebang, G.M.; Andrews, C.W.; Alberti, J.G.; Bambal, R.; Chamberlain, S.D.; Davis-Ward, R.G.; Dickson, H.D.; Hassler, D.F.; Hornberger, K.R.; Jackson, J.R.; Kuntz, K.W.; Lansing, T.J.; Mook, R.A.; Nailor, K.E.; Pobanz, M.A.; Smith, S.C.; Sung, C.M.; Cheung, M.
Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding
Bioorg. Med. Chem. Lett.
19
1694-1697
2009
Homo sapiens, Homo sapiens (P53350), Homo sapiens (Q9H4B4)
Uckun, F.M.; Ozer, Z.; Qazi, S.; Tuel-Ahlgren, L.; Mao, C.
Polo-like-kinase 1 (PLK1) as a molecular target to overcome SYK-mediated resistance of B-lineage acute lymphoblastic leukaemia cells to oxidative stress
Br. J. Haematol.
148
714-725
2010
Homo sapiens (P53350), Homo sapiens
Duan, Z.; Ji, D.; Weinstein, E.J.; Liu, X.; Susa, M.; Choy, E.; Yang, C.; Mankin, H.; Hornicek, F.J.
Lentiviral shRNA screen of human kinases identifies PLK1 as a potential therapeutic target for osteosarcoma
Cancer Lett.
293
220-229
2010
Homo sapiens (P53350), Homo sapiens
Nappi, T.C.; Salerno, P.; Zitzelsberger, H.; Carlomagno, F.; Salvatore, G.; Santoro, M.
Identification of Polo-like kinase 1 as a potential therapeutic target in anaplastic thyroid carcinoma
Cancer Res.
69
1916-1923
2009
Homo sapiens (P53350)
Gleixner, K.V.; Ferenc, V.; Peter, B.; Gruze, A.; Meyer, R.A.; Hadzijusufovic, E.; Cerny-Reiterer, S.; Mayerhofer, M.; Pickl, W.F.; Sillaber, C.; Valent, P.
Polo-like kinase 1 (Plk1) as a novel drug target in chronic myeloid leukemia: overriding imatinib resistance with the Plk1 inhibitor BI 2536
Cancer Res.
70
1513-1523
2010
Homo sapiens (P53350), Homo sapiens
Schmit, T.L.; Zhong, W.; Nihal, M.; Ahmad, N.
Polo-like kinase 1 (Plk1) in non-melanoma skin cancers
Cell Cycle
8
2697-2702
2009
Homo sapiens (P53350), Homo sapiens
Keppner, S.; Proschak, E.; Schneider, G.; Spaenkuch, B.
Identification and validation of a potent type II inhibitor of inactive polo-like kinase 1
ChemMedChem
4
1806-1809
2009
Homo sapiens (P53350)
Shi, W.; Alajez, N.M.; Bastianutto, C.; Hui, A.B.; Mocanu, J.D.; Ito, E.; Busson, P.; Lo, K.W.; Ng, R.; Waldron, J.; OSullivan, B.; Liu, F.F.
Significance of Plk1 regulation by miR-100 in human nasopharyngeal cancer
Int. J. Cancer
126
2036-2048
2010
Homo sapiens (P53350), Homo sapiens
Vitour, D.; Dabo, S.; Ahmadi Pour, M.; Vilasco, M.; Vidalain, P.O.; Jacob, Y.; Mezel-Lemoine, M.; Paz, S.; Arguello, M.; Lin, R.; Tangy, F.; Hiscott, J.; Meurs, E.F.
Polo-like kinase 1 (PLK1) regulates interferon (IFN) induction by MAVS
J. Biol. Chem.
284
21797-21809
2009
Homo sapiens (P53350)
Beria, I.; Ballinari, D.; Bertrand, J.A.; Borghi, D.; Bossi, R.T.; Brasca, M.G.; Cappella, P.; Caruso, M.; Ceccarelli, W.; Ciavolella, A.; Cristiani, C.; Croci, V.; De Ponti, A.; Fachin, G.; Ferguson, R.D.; Lansen, J.; Moll, J.K.; Pesenti, E.; Posteri, H.; Perego, R.; Rocchetti, M.; Storici, P.; Volpi, D.
Identification of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as a new class of orally and selective Polo-like kinase 1 inhibitors
J. Med. Chem.
53
3532-3551
2010
Homo sapiens (P53350), Homo sapiens (Q9H4B4), Homo sapiens (Q9NYY3)
Wang, W.S.; Lee, M.S.; Tseng, C.E.; Liao, I.H.; Huang, S.P.; Lin, R.I.; Li, C.
Interaction between human papillomavirus type 5 E2 and polo-like kinase 1
J. Med. Virol.
81
536-544
2009
Homo sapiens (P53350), Homo sapiens
Kishi, K.; van Vugt, M.A.; Okamoto, K.; Hayashi, Y.; Yaffe, M.B.
Functional dynamics of Polo-like kinase 1 at the centrosome
Mol. Cell. Biol.
29
3134-3150
2009
Homo sapiens (P53350)
Benoit, D.S.; Henry, S.M.; Shubin, A.D.; Hoffman, A.S.; Stayton, P.S.
pH-responsive polymeric sirna carriers sensitize multidrug resistant ovarian cancer cells to doxorubicin via knockdown of polo-like kinase 1
Mol. Pharm.
7
442-455
2010
Homo sapiens (P53350)
Sun, D.; Luthra, P.; Li, Z.; He, B.
PLK1 down-regulates parainfluenza virus 5 gene expression
PLoS Pathog.
5
e1000525
2009
Homo sapiens (P53350), Homo sapiens
Park, J.E.; Li, L.; Park, J.; Knecht, R.; Strebhardt, K.; Yuspa, S.H.; Lee, K.S.
Direct quantification of polo-like kinase 1 activity in cells and tissues using a highly sensitive and specific ELISA assay
Proc. Natl. Acad. Sci. USA
106
1725-1730
2009
Mus musculus, Homo sapiens (P53350), Homo sapiens
Sledz, P.; Stubbs, C.J.; Lang, S.; Yang, Y.; McKenzie, G.; Venkitaraman, A.; Hyvnen, M.; Abell, C.
From crystal packing to molecular recognition: Prediction and discovery of a binding site on the surface of polo-like kinase 1
Angew. Chem.
50
4003-4006
2011
Homo sapiens (P53350)
Caruso, M.; Valsasina, B.; Ballinari, D.; Bertrand, J.; Brasca, M.G.; Caldarelli, M.; Cappella, P.; Fiorentini, F.; Gianellini, L.M.; Scolaro, A.; Beria, I.
5-(2-amino-pyrimidin-4-yl)-1H-pyrrole and 2-(2-amino-pyrimidin-4-yl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one derivatives as new classes of selective and orally available Polo-like kinase 1 inhibitors
Bioorg. Med. Chem. Lett.
22
96-101
2012
Homo sapiens (P53350)
Bowers, S.; Truong, A.P.; Ye, M.; Aubele, D.L.; Sealy, J.M.; Neitz, R.J.; Hom, R.K.; Chan, W.; Dappen, M.S.; Galemmo, R.A.; Konradi, A.W.; Sham, H.L.; Zhu, Y.L.; Beroza, P.; Tonn, G.; Zhang, H.; Hoffman, J.; Motter, R.; Fauss, D.; Tanaka, P.; Bova, M.P.; Ren, Z.; Tam, D.; Ruslim, L.; Baker, J.; Pandya, D.; Diep, L.; F, F.i.
Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors
Bioorg. Med. Chem. Lett.
23
2743-2749
2013
Homo sapiens (P53350), Homo sapiens (Q9NYY3)
Murugan, R.N.; Park, J.E.; Lim, D.; Ahn, M.; Cheong, C.; Kwon, T.; Nam, K.Y.; Choi, S.H.; Kim, B.Y.; Yoon, D.Y.; Yaffe, M.B.; Yu, D.Y.; Lee, K.S.; Bang, J.K.
Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1
Bioorg. Med. Chem.
21
2623-2634
2013
Homo sapiens (P53350)
Lera, R.F.; Burkard, M.E.
High mitotic activity of Polo-like kinase 1 is required for chromosome segregation and genomic integrity in human epithelial cells
J. Biol. Chem.
287
42812-42825
2012
Homo sapiens (P53350), Homo sapiens
Liu, D.; Davydenko, O.; Lampson, M.A.
Polo-like kinase-1 regulates kinetochore-microtubule dynamics and spindle checkpoint silencing
J. Cell Biol.
198
491-499
2012
Homo sapiens (P53350)
Chen, D.X.; Huang, J.; Liu, M.; Xu, Y.G.; Jiang, C.
Design, synthesis, and evaluation of non-ATP-competitive small-molecule polo-like kinase 1 (Plk1) inhibitors
Arch. Pharm.
348
2-9
2015
Homo sapiens (P53350)
O'Connor, A.; Maffini, S.; Rainey, M.D.; Kaczmarczyk, A.; Gaboriau, D.; Musacchio, A.; Santocanale, C.
Requirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpoint
Biol. Open
5
11-19
2015
Homo sapiens (P53350)
Liu, M.; Huang, J.; Chen, D.X.; Jiang, C.
Identification of indole-3-carboxylic acids as non-ATP-competitive Polo-like kinase 1 (Plk1) inhibitors
Bioorg. Med. Chem. Lett.
25
431-434
2015
Homo sapiens (P53350)
Xiao, D.; Yue, M.; Su, H.; Ren, P.; Jiang, J.; Li, F.; Hu, Y.; Du, H.; Liu, H.; Qing, G.
Polo-like kinase-1 regulates Myc stabilization and activates a feedforward circuit promoting tumor cell survival
Mol. Cell
64
493-506
2016
Homo sapiens (P53350), Homo sapiens
Zhao, X.Z.; Hymel, D.; Burke, T.R.
Application of oxime-diversification to optimize ligand interactions within a cryptic pocket of the polo-like kinase 1 polo-box domain
Bioorg. Med. Chem. Lett.
26
5009-5012
2016
Homo sapiens (P53350)
Yu, X.; Li, Y.; Lou, Y.; Wang, T.
Molecular design and engineering of phosphopeptide ligands to target lung cancer polo-like kinase
Biotechnol. Bioprocess Eng.
22
218-224
2017
Homo sapiens (P53350)
-
Wu, J.; Ivanov, A.I.; Fisher, P.B.; Fu, Z.
Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling
eLife
5
e10734
2016
Homo sapiens (P53350)
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