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Information on EC 2.7.1.32 - choline kinase and Organism(s) Homo sapiens and UniProt Accession P35790
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2.7.1.32 choline kinaseIUBMB Comments
Ethanolamine and its methyl and ethyl derivatives can also act as acceptors.
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Word Map
- 2.7.1.32
- phosphatidylcholine
- phospholipid
- phosphocholine
- cytidylyltransferase
- cdp-choline
- phosphorylcholine
- phosphatidylethanolamine
-
ctp:phosphocholine
-
cholinephosphotransferase
-
kennedy
-
cholinephosphate
- glycerophosphocholine
- phosphatidate
-
choline-containing
- hemicholinium-3
- phosphoethanolamine
-
bispyridinium
-
3hcholine
-
2.7.7.15
-
ptdcho
- diagnostics
- medicine
- 1,2-diacylglycerol
- pcyt1a
- drug development
- cdp-ethanolamine
- biotechnology
-
2.7.8.2
-
phosphatidylcholine-specific
-
methyl-3hcholine
-
methyl-14ccholine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
choline kinase, choline kinase alpha, chokalpha, choline kinase beta, choline/ethanolamine kinase, chk-alpha, chokalpha1, ck-alpha, schok, choline kinase-alpha, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CHOKalpha1
CHETK-alpha
-
-
-
-
ChoK
ChoKalpha
choline kinase
-
-
choline kinase alpha
choline phosphokinase
-
-
-
-
choline-ethanolamine kinase
-
-
-
-
choline/ethanolamine kinase
-
-
-
-
EtnK
-
-
-
-
kinase, choline (phosphorylating)
-
-
-
-
ChoK
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + choline = ADP + phosphocholine
reaction mechanism of choline kinase alpha, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
ATP:choline phosphotransferase
Ethanolamine and its methyl and ethyl derivatives can also act as acceptors.
CAS REGISTRY NUMBER
COMMENTARY
9026-67-9
-
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 + choline
ADP + phosphocholine
transfer of the gamma-phosphoryl group of ATP
-
-
?
ATP + choline
ADP + O-phosphocholine
-
-
-
-
?
ATP + choline
ADP + O-phosphocholine
-
initial enzyme of the CDP-choline pathway and the CDP-ethanolamine pathway
-
-
?
ATP + choline
ADP + O-phosphocholine
-
choline pathway or CDP-ethanolamine pathway is so-called Kennedy pathway
-
-
?
ATP + choline
ADP + O-phosphocholine
-
initial step of the CDP-choline pathway, that yields phosphatidylcholine as final product, involved in mitogenic signaling transduction, possible role in carcinogenesis
-
-
?
ATP + choline
ADP + O-phosphocholine
initial step of the Kennedy pathway, that yields phosphatidylcholine as final product, involved in mitogenic signaling transduction, the product O-phosphocholine serves as second messenger and is essential for cell growth, enzyme plays a role in tumor generation
-
-
?
additional information
?
-
usage of a coupled assay method with pyruvate kinase, and lactate dehydrogenase, at pH 7.5 and 37°C
-
-
-
additional information
?
-
-
usage of a coupled assay method with pyruvate kinase, and lactate dehydrogenase, at pH 7.5 and 37°C
-
-
-
additional information
?
-
-
microarray analysis detected changes in the expression of 33 proliferation-related genes with Chk down-regulation
-
-
?
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
additional information
?
-
-
microarray analysis detected changes in the expression of 33 proliferation-related genes with Chk down-regulation
-
-
?
ATP + choline
ADP + O-phosphocholine
-
initial enzyme of the CDP-choline pathway and the CDP-ethanolamine pathway
-
-
?
ATP + choline
ADP + O-phosphocholine
-
choline pathway or CDP-ethanolamine pathway is so-called Kennedy pathway
-
-
?
ATP + choline
ADP + O-phosphocholine
-
initial step of the CDP-choline pathway, that yields phosphatidylcholine as final product, involved in mitogenic signaling transduction, possible role in carcinogenesis
-
-
?
ATP + choline
ADP + O-phosphocholine
initial step of the Kennedy pathway, that yields phosphatidylcholine as final product, involved in mitogenic signaling transduction, the product O-phosphocholine serves as second messenger and is essential for cell growth, enzyme plays a role in tumor generation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1S)-1-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-3-[2-[(oxan-4-yl)oxy]phenyl]-1-phenylpropan-1-ol
-
(4-methyl-1,4-diazepan-1-yl)(4'-((4-methyl-1,4-diazepan-1-yl)-methyl)-[1,1'-biphenyl]-4-yl)methanone
-
1,1',1''-(benzene-1,3,5-triylmethylene)tris[(4-dimethylamino)pyridinium] tribromide
-
1,1',1''-(benzene-1,3,5-triylmethylene)tris[4-(3,5-dichloro-N-methylanilino)pyridinium] tribromide
-
1,1',1''-(benzene-1,3,5-triylmethylene)tris[4-(4-chloro-N-methylanilino)pyridinium] tribromide
-
1,1',1''-(benzene-1,3,5-triylmethylene)tris[4-(N-methylanilino)pyridinium] tribromide
-
1,1',1''-(benzene-1,3,5-triylmethylene)tris[4-(piperidino)pyridinium] tribromide
-
1,1',1''-(benzene-1,3,5-triylmethylene)tris[4-(pyrrolidino)pyridinium] tribromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(3-hydroxyquinuclidinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-((4-chlorophenyl)(methyl)amino)pyridinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-((4-chlorophenyl)(methyl)amino)quinolinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(azepan-1-yl)-7-chloroquinolinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(azepan-1-yl)quinolinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(dimethylamino)pyridinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(methyl(phenyl)amino)quinolinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(pyrrolidin-1-yl)pyridinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(7-chloro-4-((4-chlorophenyl)(methyl)amino)quinolinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(7-chloro-4-(methyl(phenyl)amino)quinolinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(7-chloro-4-(pyrrolidin-1-yl)quinolinium) bromide
-
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(quinuclidinium) bromide
-
1,1'-(benzene-1,3-diylmethylene)bis[(4-dimethylamino)pyridinium] dibromide
-
1,1'-(benzene-1,3-diylmethylene)bis[4-(N-methylanilino)pyridinium] dibromide
-
1,1'-(benzene-1,3-diylmethylene)bis[4-(piperidino)pyridinium] dibromide
-
1,1'-(benzene-1,3-diylmethylene)bis[4-(pyrrolidino)pyridinium] dibromide
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[4-(dimethylamino)quinolinium]
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[4-(phenylamino)quinolinium]
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[4-[(4-chlorophenyl)(methyl)amino]quinolinium]
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[4-[methyl(phenyl)amino]quinolinium]
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-amino-4-[(4-chlorophenyl)(methyl)amino]-8-methylquinolinium]
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-amino-8-methyl-4-[methyl(phenyl)amino]quinolinium]
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-chloro-4-(dimethylamino)quinolinium]
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-chloro-4-[(4-chlorophenyl)(methyl)amino]quinolinium]
-
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-chloro-4-[methyl(phenyl)amino]quinolinium]
-
1,1'-biphenyl-3,3'-diylbis[4-[(4-chlorophenyl)(methyl)amino]quinolinium]
-
1,1'-biphenyl-3,3'-diylbis[7-amino-4-[(4-chlorophenyl)(methyl)amino]-8-methylquinolinium]
-
1,1'-biphenyl-3,3'-diylbis[7-amino-8-methyl-4-[methyl(phenyl)amino]quinolinium]
-
1,1'-biphenyl-3,3'-diylbis[7-chloro-4-[(4-chlorophenyl)(methyl)amino]quinolinium]
-
1,1'-biphenyl-3,3'-diylbis[7-chloro-4-[methyl(phenyl)amino]quinolinium]
-
1,1'-biphenyl-4,4'-diylbis[4-[(4-chlorophenyl)(methyl)amino]quinolinium]
-
1,1'-biphenyl-4,4'-diylbis[7-amino-4-[(4-chlorophenyl)(methyl)amino]-8-methylquinolinium]
-
1,1'-biphenyl-4,4'-diylbis[7-amino-8-methyl-4-[methyl(phenyl)amino]quinolinium]
-
1,1'-biphenyl-4,4'-diylbis[7-chloro-4-[(4-chlorophenyl)(methyl)amino]quinolinium]
-
1,1'-biphenyl-4,4'-diylbis[7-chloro-4-[methyl(phenyl)amino]quinolinium]
-
1,1'-[butane-1,4-diylbis[(4,1-phenylene)methylene]]bis[4-(dimethylamino)pyridin-1-ium]
-
1-(4-(4-[(3-aminophenoxy)methyl]phenethyl)benzyl)-4-(dimethylamino)pyridinium bromide
21.9% inhibition at 0.05 mM
1-(4-[4-[(3-hydroxyphenylamino)methyl]phenethyl]-benzyl)-4-(pyrrolidin-1-yl)pyridinium bromide
13.6% inhibition at 0.05 mM
1-(4-[4-[(6-amino-3H-purin-3-yl)methyl]phenethyl]benzyl)-4-pyrrolidinopyridinium bromide
0.1% inhibition at 0.01 mM, 24.8% inhibition at 0.05 mM
1-(4-[4-[(6-amino-3H-purin-3-yl)methyl]phenyl]benzyl)-4-(dimethylamino)pyridinium bromide
62.3% inhibition at 0.01 mM, 71.4% inhibition at 0.05 mM
1-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenethyl]benzyl)-4-(dimethylamino)pyridinium bromide
38.6% inhibition at 0.01 mM, 81% inhibition at 0.05 mM
1-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenethyl]benzyl)-4-pyrrolidinopyridinium bromide
28.6% inhibition at 0.01 mM, 46.9% inhibition at 0.05 mM
1-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]benzyl)-4-(dimethylamino)pyridinium bromide
37.6% inhibition at 0.01 mM, 51% inhibition at 0.05 mM
1-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]benzyl)-4-pyrrolidinopyridinium bromide
50.2% inhibition at 0.01 mM, 72.8% inhibition at 0.05 mM
1-([4'-[(3-aminophenoxy)methyl]biphenyl-4-yl]methyl)-4-(dimethylamino)pyridinium bromide
79.8% inhibition at 0.05 mM
1-([4'-[(3-aminophenoxy)methyl]biphenyl-4-yl]methyl)-4-(pyrrolidin-1-yl)pyridinium bromide
20.8% inhibition at 0.05 mM
1-([4'-[(3-hydroxyphenylamino)methyl]biphenyl-4-yl]-methyl)-4-(pyrrolidin-1-yl)-pyridinium bromide
28.2% inhibition at 0.05 mM
1-methyl-4-((4'-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-4-yl)-methyl)-1,4-diazepane
-
1-methyl-4-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methyl)-1,4-diazepane
-
1-[(4-[4-[4-([4-[(4-chlorophenyl)(methyl)amino]pyridin-1-ium-1-yl]methyl)phenyl]butyl]phenyl)methyl]-4-(dimethylamino)pyridin-1-ium
-
1-[(4-[4-[4-([4-[(4-chlorophenyl)(methyl)amino]pyridin-1-ium-1-yl]methyl)phenyl]butyl]phenyl)methyl]-4-(dimethylamino)pyridin-1-ium dibromide
-
1-[4'-[(6-amino-9H-purin-9-yl)methyl][1,1'-biphenyl]-4-yl]-4-(dimethylamino)pyridin-1-ium bromide
-
1-[4-(4-[4-[(3-aminophenoxy)methyl]phenyl]butyl)-benzyl]-4-(pyrrolidin-1-yl)pyridinium bromide
21.6% inhibition at 0.05 mM
1-[4-(4-[4-[(3-hydroxyphenylamino)methyl]phenyl]-butyl)benzyl]-4-(pyrrolidin-1-yl)pyridinium bromide
18% inhibition at 0.05 mM
1-[4-(4-[4-[(6-amino-3H-purin-3-yl)methyl]phenyl]butyl)benzyl]-4-(dimethylamino)pyridinium bromide
61.3% inhibition at 0.01 mM, 68.2% inhibition at 0.05 mM
1-[4-(4-[4-[(6-amino-3H-purin-3-yl)methyl]phenyl]butyl)benzyl]-4-pyrrolidinopyridinium bromide
22.6% inhibition at 0.01 mM, 59.9% inhibition at 0.05 mM
1-[4-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]butyl)benzyl]-4-(dimethylamino)pyridinium bromide
66.7% inhibition at 0.01 mM, 89.7% inhibition at 0.05 mM
1-[4-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]butyl)benzyl]-4-pyrrolidinopyridinium bromide
36.9% inhibition at 0.01 mM, 41.9% inhibition at 0.05 mM
1-[4-[(3-aminophenoxy)methyl]benzyl]-4-(dimethylamino)pyridinium bromide
37.7% inhibition at 0.05 mM
1-[4-[(3-aminophenoxy)methyl]benzyl]-4-(pyrrolidin-1-yl)pyridinium bromide
12.9% inhibition at 0.05 mM
1-[4-[(3-hydroxyphenylamino)methyl]benzyl]-4-(pyrrolidin-1-yl)pyridinium bromide
41.3% inhibition at 0.05 mM
1-[4-[(6-amino-3H-purin-3-yl)methyl]benzyl]-4-(dimethylamino)pyridinium bromide
25% inhibition at 0.01 mM, 50.2% inhibition at 0.05 mM
1-[4-[(6-amino-9H-purin-9-yl)methyl]benzyl]-4-(dimethylamino)pyridinium bromide
46.7% inhibition at 0.01 mM, 54.1% inhibition at 0.05 mM
1-[4-[(6-amino-9H-purin-9-yl)methyl]benzyl]-4-pyrrolidinopyridinium bromide
27% inhibition at 0.05 mM
1-[[4-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]butyl)phenyl]methyl]-4-(dimethylamino)pyridin-1-ium bromide
-
1-[[4-[4-[[4-(4-chloro-N-methylanilino)quinolin-1-ium-1-yl]methyl]phenyl]phenyl]methyl]-N-(4-chlorophenyl)-N-methylquinolin-1-ium-4-amine
i.e. TCD-717 or RSM-932A, strong inhibition of ChoKalpha, TCD-717 does not bind directly in the choline pocket but rather in a proximal location near the surface of the enzyme. Most notably, residues Tyr148, Ala176, Met177, Glu180, Phe200, Pro201, Trp248, Thr252, Tyr256, Glu332, Tyr333, Phe341, and Leu419 serve to orient and hold TCD-717 in place. Interaction of TCD-717 with ChoKalpha is driven by hydrophobic interactions across the N- and C-terminal domains. Binding of TCD-717 induces conformational changes compared to the unbound ChoKalpha structure. TCD-717 has completed phase I clinical trials
2'-fluoro-4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
-
4,4'-((2,3-difluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis-(1-methyl-1,4-diazepane)
-
4,4'-((2-fluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis(1-methyl-1,4-diazepane)
-
4,4'-((3,5-difluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis-(1-methyl-1,4-diazepane)
-
4,4'-((3-chloro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis(1-methyl-1,4-diazepane)
-
4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
-
4-(4-chloro-N-methylanilino)-1-(4-[4-[(4-dimethylaminopyridinium-1-yl)methyl]phenethyl]benzyl)pyridinium dibromide
-
4-(4-chloro-N-methylanilino)-1-(4-[4-[(4-dimethylaminopyridinium-1-yl)methyl]phenyl]benzyl)pyridinium dibromide
-
4-(4-chloro-N-methylanilino)-1-(4-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]phenethyl]benzyl)pyridinium dibromide
-
4-(4-chloro-N-methylanilino)-1-(4-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]phenyl]benzyl)pyridinium dibromide
-
4-(4-chloro-N-methylanilino)-1-[4-(4-[4-[(4-dimethylaminopyridinium-1-yl)methyl]phenyl]butyl)benzyl]pyridinium dibromide
-
4-(4-chloro-N-methylanilino)-1-[4-(4-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]phenyl]butyl)benzyl]pyridinium dibromide
-
4-(4-chloro-N-methylanilino)-1-[4-[(4-dimethylaminopyridinium-1-yl)methyl]benzyl]pyridinium dibromide
-
4-(4-chloro-N-methylanilino)-1-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]benzyl]pyridinium dibromide
-
4-(dimethylamino)-1-(4-(3-(4-(((3-hydroxyphenyl)amino)methyl)phenyl)propyl)benzyl)pyridin-1-ium bromide
12.9% inhibition at 0.05 mM
4-(dimethylamino)-1-(4-(4-(((3-hydroxyphenyl)amino)methyl)benzyl)benzyl)pyridin-1-ium bromide
39.5% inhibition at 0.05 mM
4-(dimethylamino)-1-(4-[4-[(4-pyrrolidinopyridinium-1-yl)-methyl]phenethyl]benzyl)pyridinium dibromide
-
4-(dimethylamino)-1-(4-[4-[(4-pyrrolidinopyridinium-1-yl)-methyl]phenyl]benzyl)pyridinium dibromide
-
4-(dimethylamino)-1-({4-[(3-hydroxyphenylamino)-methyl]biphenyl-4-yl}methyl)pyridinium bromide
66.2% inhibition at 0.05 mM
4-(dimethylamino)-1-[4-(4-[4-[(4-pyrrolidinopyridinium-1-yl)-methyl]phenyl]butyl)benzyl]pyridinium dibromide
-
4-(dimethylamino)-1-[4-[(3-hydroxyphenylamino)-methyl]benzyl]pyridinium bromide
52.4% inhibition at 0.05 mM
4-(dimethylamino)-1-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]-benzyl]pyridinium dibromide
-
4-[(4-chlorophenyl)(methyl)amino]-1-[(4'-[[4-(dimethylamino)phenyl]methyl][1,1'-biphenyl]-4-yl)methyl]pyridin-1-ium bromide
-
6-amino-3-[(4'-[[4-(dimethylamino)pyridin-1-ium-1-yl]methyl][1,1'-biphenyl]-4-yl)methyl]-9H-purin-3-ium
-
7-chloro-1-(4-[2-[4-(7-chloro-5-pyrrolidin-1-ylquinolinium-1-yl)phenyl]ethyl]phenyl)-4-pyrrolidin-1-ylquinolinium
-
methyl 4'-((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-4-carboxylate
-
(1-azabicyclo[2.2.2]octan-3-yl)bis(5-chlorothiophen-2-yl)methanol
precursor of (1S)-1-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-3-[2-[(oxan-4-yl)oxy]phenyl]-1-phenylpropan-1-ol, inhibits competitively against ATP, but not against choline
(1S)-1-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-3-[2-[(oxan-4-yl)oxy]phenyl]-1-phenylpropan-1-ol
a structure-directed, selective ChoKalpha inhibitor. Treatment of HeLa cells and other cancer cells with the compound leads to a substantial reduction in the pCho level, and causes a reversible growth arrest but not cell death
(4-methyl-1,4-diazepan-1-yl)(4'-((4-methyl-1,4-diazepan-1-yl)-methyl)-[1,1'-biphenyl]-4-yl)methanone
-
1,1'-(benzene-1,3-diyldimethanediyl)bis(4-piperidin-1-ylpyridinium) dibromide
-
IC50: 0.0528 mM
1,1'-(benzene-1,3-diyldimethanediyl)bis(4-pyrrolidin-1-ylpyridinium) dibromide
-
IC50: 0.0842 mM
1,1'-(benzene-1,3-diyldimethanediyl)bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0084 mM
1,1'-(benzene-1,3-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0072 mM
1,1'-(benzene-1,3-diyldimethanediyl)bis[4-[(phenylamino)methyl]pyridinium] dibromide
-
IC50: 0.0375 mM
1,1'-(benzene-1,4-diyldimethanediyl)bis(4-piperidin-1-ylpyridinium) dibromide
-
IC50: 0.0377 mM
1,1'-(benzene-1,4-diyldimethanediyl)bis(4-pyrrolidin-1-ylpyridinium) dibromide
-
IC50: 0.024 mM
1,1'-(benzene-1,4-diyldimethanediyl)bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0097 mM
1,1'-(benzene-1,4-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0029 mM
1,1'-(benzene-1,4-diyldimethanediyl)bis[4-[(phenylamino)methyl]pyridinium] dibromide
-
IC50: 0.015 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-amino-3-methylquinolinium) dibromide
-
IC50: 0.0119 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-amino-7-chloroquinolinium) dibromide
-
IC50: 0.0206 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-aminoquinolinium) dibromide
-
IC50: 0.0012 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-azepan-1-ylquinolinium) dibromide
-
IC50: 0.0005 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-piperidin-1-ylpyridinium) dibromide
-
IC50: 0.0019 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-pyrrolidin-1-ylpyridinium) dibromide
-
IC50: 0.0058 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0026 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0015 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
-
IC50: 0.0021 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(7-amino-4-[[(4-chlorophenyl)amino]methyl]-8-methylquinolinium) dibromide
-
IC50: 0.147 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(7-chloro-4-pyrrolidin-1-ylquinolinium) dibromide
-
IC50: 0.0012 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(7-chloro-4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
-
IC50: 0.0057 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[4-(dimethylamino)quinolinium] dibromide
-
IC50: 0.0044 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[4-(phenylamino)quinolinium] dibromide
-
IC50: 0.0013 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[4-[(phenylamino)methyl]pyridinium] dibromide
-
IC50: 0.00043 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.0004 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[7-amino-8-methyl-4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.0568 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[7-chloro-4-(dimethylamino)quinolinium] dibromide
-
IC50: 0.0096 mM
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[7-chloro-4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.0031 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-amino-3-methylquinolinium) dibromide
-
IC50: above 0.2 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-amino-7-chloroquinolinium) dibromide
-
IC50: 0.0633 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-aminoquinolinium) dibromide
-
IC50: 0.0811 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-azepan-1-ylquinolinium) dibromide
-
IC50: 0.0022 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-piperidin-1-ylpyridinium) dibromide
-
IC50: 0.0088 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-pyrrolidin-1-ylpyridinium) dibromide
-
IC50: 0.0111 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0034 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0018 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
-
IC50: 0.002 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(7-amino-4-[[(4-chlorophenyl)amino]methyl]-8-methylquinolinium) dibromide
-
IC50: 0.0461 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(7-chloro-4-pyrrolidin-1-ylquinolinium) dibromide
-
IC50: 0.0198 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(7-chloro-4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
-
IC50: 0.0114 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[4-(dimethylamino)quinolinium] dibromide
-
IC50: 0.0397 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[4-(phenylamino)quinolinium] dibromide
-
IC50: 0.0178 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[4-[(phenylamino)methyl]pyridinium] dibromide
-
IC50: 0.0043 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.003 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[7-amino-8-methyl-4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.0961 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[7-chloro-4-(dimethylamino)quinolinium] dibromide
-
IC50: 0.0206 mM
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[7-chloro-4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.0114 mM
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-piperidin-1-ylpyridinium) dibromide
-
IC50: 0.098 mM
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-pyrrolidin-1-ylpyridinium) dibromide
-
IC50: above 0.1 mM
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis[4-[(phenylamino)methyl]pyridinium] dibromide
-
IC50: above 0.1 mM
1,1'-[butane-1,4-diylbis[(4,1-phenylene)methylene]]bis[4-(dimethylamino)pyridin-1-ium]
a less toxic derivative of hemicholinium-3, it inhibits endogenous ChoKbeta activity and suppress breast cancer, colon cancer, and epidermoid carcinoma xenograft growth in vivo
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(4-amino-7-chloroquinolinium) dibromide
-
IC50: above 0.2 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(4-aminoquinolinium) dibromide
-
IC50: 0.08 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(4-azepan-1-ylquinolinium) dibromide
-
IC50: 0.006 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
-
IC50: 0.0048 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(7-amino-4-[[(4-chlorophenyl)amino]methyl]-8-methylquinolinium) dibromide
-
IC50: 0.0575 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(7-chloro-4-pyrrolidin-1-ylquinolinium) dibromide
-
IC50: 0.001 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(7-chloro-4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
-
IC50: 0.0057 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[4-(dimethylamino)quinolinium] dibromide
-
IC50: 0.0102 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[4-(phenylamino)quinolinium] dibromide
-
IC50: 0.0023 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.0014 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[7-amino-8-methyl-4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.133 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[7-chloro-4-(dimethylamino)quinolinium] dibromide
-
IC50: 0.009 mM
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[7-chloro-4-[(phenylamino)methyl]quinolinium] dibromide
-
IC50: 0.0035 mM
1,1'-[[1,1'-biphenyl]-4,4'-diylbis(methylene)]bis[4-[(4-chlorophenyl)(methyl)amino]quinolin-1-ium]
RSM-932A or TDC-717, a potential cancer therapeutic agent targeting choline metabolism, strong inhibition
1-([4'-[(6-amino-9H-purin-9-yl)methyl][1,1'-biphenyl]-4-yl]methyl)-4-(dimethylamino)pyridin-1-ium bromide
-
1-([4'-[(6-amino-9H-purin-9-yl)methyl][1,1'-biphenyl]-4-yl]methyl)-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
-
1-([4-[(6-amino-9H-purin-9-yl)methyl]phenyl]methyl)-4-(dimethylamino)pyridin-1-ium bromide
-
1-([4-[(6-amino-9H-purin-9-yl)methyl]phenyl]methyl)-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
-
1-([4-[2-(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)ethyl]phenyl]methyl)-4-(dimethylamino)pyridin-1-ium bromide
-
1-([4-[2-(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)ethyl]phenyl]methyl)-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
-
1-([4-[4-(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)butyl]phenyl]methyl)-4-(dimethylamino)pyridin-1-ium bromide
-
1-([4-[4-(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)butyl]phenyl]methyl)-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
-
1-methyl-4-((4'-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-4-yl)-methyl)-1,4-diazepane
-
1-methyl-4-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methyl)-1,4-diazepane
-
1-[(4'-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl][1,1'-biphenyl]-4-yl)methyl]-4-(dimethylamino)pyridin-1-ium bromide
-
1-[(4'-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl][1,1'-biphenyl]-4-yl)methyl]-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
-
1-[(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)methyl]-4-(dimethylamino)pyridin-1-ium bromide
-
1-[(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)methyl]-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
-
1-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]methanamine
analysis of the enzyme bound structure, PDB ID 5EQE
1-[[4-(2-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]ethyl)phenyl]methyl]-4-(dimethylamino)pyridin-1-ium bromide
-
1-[[4-(2-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]ethyl)phenyl]methyl]-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
-
1-[[4-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]butyl)phenyl]methyl]-4-(dimethylamino)pyridin-1-ium bromide
-
1-[[4-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]butyl)phenyl]methyl]-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
-
12,19-diaza-1,8-diazoniapentacyclo[18.2.2.23,6.28,11.214,17]triaconta-1(22),3,5,8,10,14,16,20,23,25,27,29-dodecaene dibromide
-
IC50: 0.0132 mM
12,21-diaza-1,8-diazoniapentacyclo[20.2.2.23,6.28,11.014,19]triaconta-1(24),3,5,8,10,14,16,18,22,25,27,29-dodecaene dibromide
-
IC50: 0.0021 mM
14,21-diaza-1,10-diazoniapentacyclo[20.2.2.210,13.216,19.03,8]triaconta-1(24),3,5,7,10,12,16,18,22,25,27,29-dodecaene dibromide
2'-fluoro-4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
-
4,4'-((2,3-difluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis-(1-methyl-1,4-diazepane)
-
4,4'-((2-fluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis(1-methyl-1,4-diazepane)
-
4,4'-((3,5-difluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis-(1-methyl-1,4-diazepane)
-
4,4'-((3-chloro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis(1-methyl-1,4-diazepane)
-
4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
-
5,10,11,16,17,22-hexahydro-6,9:18,21-diethenodibenzo[g,p][1,5,10,14]tetraazacyclooctadecine-6,21-diium dibromide
-
IC50: 0.0248 mM
5-fluorouracil
-
Investigation of the effect of combining transient siRNA-chk transfection with the anticancer drug 5-fluorouracil on cell viability and proliferation. Choline kinase down-regulation with 5-fluorouracil treatment increased cell kill in cancer cells.
6-amino-3-([4-[4-(4-[[4-(dimethylamino)pyridin-1-ium-1-yl]methyl]phenyl)butyl]phenyl]methyl)-9H-purin-3-ium
-
6-amino-3-([4-[4-(4-[[4-(pyrrolidin-1-yl)pyridin-1-ium-1-yl]methyl]phenyl)butyl]phenyl]methyl)-9H-purin-3-ium
-
6-amino-3-[(4'-[[4-(dimethylamino)pyridin-1-ium-1-yl]methyl][1,1'-biphenyl]-4-yl)methyl]-9H-purin-3-ium
-
6-amino-3-[(4-[[4-(dimethylamino)pyridin-1-ium-1-yl]methyl]phenyl)methyl]-9H-purin-3-ium
-
methyl 4'-((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-4-carboxylate
-
N-(3,5-dimethylphenyl)-2-[[5-(4-ethylphenyl)-1H-1,2,4-triazol-3-yl]sulfanyl]acetamide
CK37, identified through computational virtual screening, inhibits ChoKalpha activity both in enzymatic and in cellular assays, is able to suppress pCho production and tumor growth in vivo
hemicholinium-3
competitive inhibitor, the inhibitory effect of hemicholinium-3 is about 500times higher toward the ChoKalpha isoforms than ChoKbeta isoform
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: above 0.1 mM
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
-
IC50: 0.0482 mM
14,21-diaza-1,10-diazoniapentacyclo[20.2.2.210,13.216,19.03,8]triaconta-1(24),3,5,7,10,12,16,18,22,25,27,29-dodecaene dibromide
-
IC50: 0.0003 mM
14,21-diaza-1,10-diazoniapentacyclo[20.2.2.210,13.216,19.03,8]triaconta-1(24),3,5,7,10,12,16,18,22,25,27,29-dodecaene dibromide
-
IC50: 0.0003 mM, most potent inhibitor
hemicholinium-3
competitive inhibitor, the inhibitory effect of hemicholinium-3 is about 500times higher toward the ChoKalpha isoforms than ChoKbeta isoform
hemicholinium-3
HC-3, a substrate site inhibitor that bears structural homology to choline, which contributes to its toxicity
additional information
not inhibited by 1-[4-(4-[4-[(3-aminophenoxy)methyl]phenyl]butyl)-benzyl]-4-(dimethylamino)pyridinium bromide
-
additional information
chemotherapeutic drug design has centered on stopping the catalytic activity of choline kinase and reducing the downstream metabolites it produces
-
additional information
-
chemotherapeutic drug design has centered on stopping the catalytic activity of choline kinase and reducing the downstream metabolites it produces
-
additional information
choline kinase inhibition and docking studies of a series of 6-(benzylthio)-9H-purin-9-yl-pyridinium derivatives using native ChoK from the cytosol of Hep-G2 cells and recombinantly expressed ChoKalpha, overview
-
additional information
small molecule inhibitors of choline kinase identified by fragment-based drug discovery (NMR fragment screening and competition experiments), quantification of protein-ligand affinities, overview
-
additional information
-
small molecule inhibitors of choline kinase identified by fragment-based drug discovery (NMR fragment screening and competition experiments), quantification of protein-ligand affinities, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
c-Src
isoform CHKA2 total cellular activity and protein levels are regulated by c-Src
-
epidermal growth factor receptor
isoform CHKA2 total cellular activity and protein levels are regulated by epidermal growth factor receptor. In the presence of co-transfected epidermal growth factor receptor, the activity of wild type isoform CHKA2 is increased 2.5 fold
-
additional information
-
activation of choline kinase is essential for building membranes, cell growth, cell proliferationand for rebuilding phospholipids that are degraded in the process of signal transductiony
-
additional information
-
ChoKalpha mRNA levels are increased in tumour cell lines in terms of their corresponding normal human primary BEC. ChoKalpha is overexpressed with a consequent increase in phosphorylcholine production in lung-cancer cells.
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.4
ATP
isoform ChoKalpha2 mutant F352L, pH and temperature not specified in the publication
0.4
ATP
wild type isoform ChoKalpha2, pH and temperature not specified in the publication
0.55
ATP
isoform ChoKalpha2 mutant F352A, pH and temperature not specified in the publication
0.76
ATP
wild type isoform ChoKalpha1, pH and temperature not specified in the publication
0.021
choline
isoform ChoKalpha2 mutant F352L, pH and temperature not specified in the publication
0.07
choline
in 100 mM Tris-HCl buffer (pH 7.5) containing 100 mM KCl, 10 mM MgCl2, 0.5 mM phosphoenolpyruvate, 0.25 mM NADH, 4 units pyruvate kinase, and 5 units lactate dehydrogenase
0.086
choline
wild type isoform ChoKalpha2, pH and temperature not specified in the publication
0.107
choline
isoform ChoKalpha2 mutant F352A, pH and temperature not specified in the publication
0.18
choline
wild type isoform ChoKalpha1, pH and temperature not specified in the publication
0.188
choline
in 100 mM Tris-HCl pH 7.5, 100 mM KCl, 10 mM MgCl2, at 25°C
0.4
ATP
wild type isoform ChoKbeta, pH and temperature not specified in the publication
0.65
ATP
isoform ChoKbeta mutant F352A, pH and temperature not specified in the publication
0.7
ATP
isoform ChoKbeta mutant F352L, pH and temperature not specified in the publication
0.033
choline
wild type isoform ChoKbeta, pH and temperature not specified in the publication
0.041
choline
isoform ChoKbeta mutant F352L, pH and temperature not specified in the publication
0.102
choline
isoform ChoKbeta mutant F352A, pH and temperature not specified in the publication
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14
choline
isoform ChoKalpha2 mutant F352L, pH and temperature not specified in the publication
47.33
choline
wild type isoform ChoKalpha2, pH and temperature not specified in the publication
49.5
choline
isoform ChoKalpha2 mutant F352A, pH and temperature not specified in the publication
71.5
choline
in 100 mM Tris-HCl buffer (pH 7.5) containing 100 mM KCl, 10 mM MgCl2, 0.5 mM phosphoenolpyruvate, 0.25 mM NADH, 4 units pyruvate kinase, and 5 units lactate dehydrogenase
76.83
choline
wild type isoform ChoKalpha1, pH and temperature not specified in the publication
2.92
choline
wild type isoform ChoKbeta, pH and temperature not specified in the publication
4.58
choline
isoform ChoKbeta mutant F352L, pH and temperature not specified in the publication
9.5
choline
isoform ChoKbeta mutant F352A, pH and temperature not specified in the publication
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00021
hemicholinium-3
wild type isoform ChoKalpha1, pH and temperature not specified in the publication
0.00023
hemicholinium-3
wild type isoform ChoKalpha2, pH and temperature not specified in the publication
0.00045
hemicholinium-3
isoform ChoKalpha2 mutant F352A, pH and temperature not specified in the publication
0.016
hemicholinium-3
isoform ChoKalpha2 mutant F352L, pH and temperature not specified in the publication
0.005
hemicholinium-3
isoform ChoKbeta mutant F352L, pH and temperature not specified in the publication
0.008
hemicholinium-3
isoform ChoKbeta mutant F352A, pH and temperature not specified in the publication
0.116
hemicholinium-3
wild type isoform ChoKbeta, pH and temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000251
(4-methyl-1,4-diazepan-1-yl)(4'-((4-methyl-1,4-diazepan-1-yl)-methyl)-[1,1'-biphenyl]-4-yl)methanone
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.00951
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(3-hydroxyquinuclidinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.00163
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-((4-chlorophenyl)(methyl)amino)pyridinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.00327
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-((4-chlorophenyl)(methyl)amino)quinolinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.00202
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(azepan-1-yl)-7-chloroquinolinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.00166
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(azepan-1-yl)quinolinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.001
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(dimethylamino)pyridinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.00685
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(methyl(phenyl)amino)quinolinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.00956
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(pyrrolidin-1-yl)pyridinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.01622
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(7-chloro-4-((4-chlorophenyl)(methyl)amino)quinolinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.00279
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(7-chloro-4-(methyl(phenyl)amino)quinolinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.00092
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(7-chloro-4-(pyrrolidin-1-yl)quinolinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.03754
1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(quinuclidinium) bromide
Homo sapiens
at pH 8.5 and 37°C
0.0006
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis(4-azepan-1-ylquinolinium)
Homo sapiens
-
0.0102
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[4-(dimethylamino)quinolinium]
Homo sapiens
-
0.0023
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[4-(phenylamino)quinolinium]
Homo sapiens
-
0.0048
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[4-[(4-chlorophenyl)(methyl)amino]quinolinium]
Homo sapiens
-
0.0014
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[4-[methyl(phenyl)amino]quinolinium]
Homo sapiens
-
0.0575
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-amino-4-[(4-chlorophenyl)(methyl)amino]-8-methylquinolinium]
Homo sapiens
-
0.133
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-amino-8-methyl-4-[methyl(phenyl)amino]quinolinium]
Homo sapiens
-
0.009
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-chloro-4-(dimethylamino)quinolinium]
Homo sapiens
-
0.0057
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-chloro-4-[(4-chlorophenyl)(methyl)amino]quinolinium]
Homo sapiens
-
0.0035
1,1'-(ethane-1,2-diyldibenzene-4,1-diyl)bis[7-chloro-4-[methyl(phenyl)amino]quinolinium]
Homo sapiens
-
0.0012
1,1'-biphenyl-3,3'-diylbis(7-chloro-4-pyrrolidin-1-ylquinolinium)
Homo sapiens
-
0.0021
1,1'-biphenyl-3,3'-diylbis[4-[(4-chlorophenyl)(methyl)amino]quinolinium]
Homo sapiens
-
0.147
1,1'-biphenyl-3,3'-diylbis[7-amino-4-[(4-chlorophenyl)(methyl)amino]-8-methylquinolinium]
Homo sapiens
-
0.0568
1,1'-biphenyl-3,3'-diylbis[7-amino-8-methyl-4-[methyl(phenyl)amino]quinolinium]
Homo sapiens
-
0.0096
1,1'-biphenyl-3,3'-diylbis[7-chloro-4-(dimethylamino)quinolinium]
Homo sapiens
-
0.0057
1,1'-biphenyl-3,3'-diylbis[7-chloro-4-[(4-chlorophenyl)(methyl)amino]quinolinium]
Homo sapiens
-
0.0031
1,1'-biphenyl-3,3'-diylbis[7-chloro-4-[methyl(phenyl)amino]quinolinium]
Homo sapiens
-
0.0198
1,1'-biphenyl-4,4'-diylbis(7-chloro-4-pyrrolidin-1-ylquinolinium)
Homo sapiens
-
0.002
1,1'-biphenyl-4,4'-diylbis[4-[(4-chlorophenyl)(methyl)amino]quinolinium]
Homo sapiens
-
0.0461
1,1'-biphenyl-4,4'-diylbis[7-amino-4-[(4-chlorophenyl)(methyl)amino]-8-methylquinolinium]
Homo sapiens
-
0.0961
1,1'-biphenyl-4,4'-diylbis[7-amino-8-methyl-4-[methyl(phenyl)amino]quinolinium]
Homo sapiens
-
0.0206
1,1'-biphenyl-4,4'-diylbis[7-chloro-4-(dimethylamino)quinolinium]
Homo sapiens
-
0.0114
1,1'-biphenyl-4,4'-diylbis[7-chloro-4-[(4-chlorophenyl)(methyl)amino]quinolinium]
Homo sapiens
-
0.0114
1,1'-biphenyl-4,4'-diylbis[7-chloro-4-[methyl(phenyl)amino]quinolinium]
Homo sapiens
-
0.00143
1-((4'-methoxy-[1,1'-biphenyl]-4-yl)methyl)-4-methyl-1,4-diazepane
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.00621
1-(4-[4-[(6-amino-3H-purin-3-yl)methyl]phenyl]benzyl)-4-(dimethylamino)pyridinium bromide
Homo sapiens
in 100 mM Tris (pH 8.5), 10 mM MgCl2, at 37°C
0.0015
1-([1,1'-biphenyl]-4-ylmethyl)-4-methyl-1,4-diazepane
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.0013
1-methyl-4-((4'-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-4-yl)-methyl)-1,4-diazepane
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.0026
1-methyl-4-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methyl)-1,4-diazepane
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.0026
1-methyl-4-(naphthalen-2-ylmethyl)-1,4-diazepane
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.0389
1-[4-(4-[4-[(6-amino-3H-purin-3-yl)methyl]phenyl]butyl)benzyl]-4-(dimethylamino)pyridinium bromide
Homo sapiens
in 100 mM Tris (pH 8.5), 10 mM MgCl2, at 37°C
0.0107
1-[4-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]butyl)benzyl]-4-(dimethylamino)pyridinium bromide
Homo sapiens
in 100 mM Tris (pH 8.5), 10 mM MgCl2, at 37°C
0.00052
1-[[4-[4-[[4-(4-chloro-N-methylanilino)quinolin-1-ium-1-yl]methyl]phenyl]phenyl]methyl]-N-(4-chlorophenyl)-N-methylquinolin-1-ium-4-amine
Homo sapiens
wild-type enzyme ChoKalpha, pH 7.5, 37°C
0.000085
2'-fluoro-4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.000233
4,4'-((2,3-difluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis-(1-methyl-1,4-diazepane)
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.000165
4,4'-((2-fluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis(1-methyl-1,4-diazepane)
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.000255
4,4'-((3,5-difluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis-(1-methyl-1,4-diazepane)
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.000268
4,4'-((3-chloro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis(1-methyl-1,4-diazepane)
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.000457
4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-1,1'-biphenyl
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.000066
4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.0007
4-(4-chloro-N-methylanilino)-1-(4-[4-[(4-dimethylaminopyridinium-1-yl)methyl]phenethyl]benzyl)pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0015
4-(4-chloro-N-methylanilino)-1-(4-[4-[(4-dimethylaminopyridinium-1-yl)methyl]phenyl]benzyl)pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0025
4-(4-chloro-N-methylanilino)-1-(4-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]phenethyl]benzyl)pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0022
4-(4-chloro-N-methylanilino)-1-(4-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]phenyl]benzyl)pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0012
4-(4-chloro-N-methylanilino)-1-[4-(4-[4-[(4-dimethylaminopyridinium-1-yl)methyl]phenyl]butyl)benzyl]pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0015
4-(4-chloro-N-methylanilino)-1-[4-(4-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]phenyl]butyl)benzyl]pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0009
4-(4-chloro-N-methylanilino)-1-[4-[(4-dimethylaminopyridinium-1-yl)methyl]benzyl]pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0006
4-(4-chloro-N-methylanilino)-1-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]benzyl]pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0012
4-(dimethylamino)-1-(4-[4-[(4-pyrrolidinopyridinium-1-yl)-methyl]phenethyl]benzyl)pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0008
4-(dimethylamino)-1-(4-[4-[(4-pyrrolidinopyridinium-1-yl)-methyl]phenyl]benzyl)pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0009
4-(dimethylamino)-1-[4-(4-[4-[(4-pyrrolidinopyridinium-1-yl)-methyl]phenyl]butyl)benzyl]pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.008
4-(dimethylamino)-1-[4-[(4-pyrrolidinopyridinium-1-yl)methyl]-benzyl]pyridinium dibromide
Homo sapiens
at pH 8.5 and 37°C
0.0015
7-((4-methyl-1,4-diazepan-1-yl)methyl)quinolone
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.001
7-chloro-1-(4-[2-[4-(7-chloro-5-pyrrolidin-1-ylquinolinium-1-yl)phenyl]ethyl]phenyl)-4-pyrrolidin-1-ylquinolinium
Homo sapiens
-
0.00495
methyl 4'-((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-4-carboxylate
Homo sapiens
at pH 7.0, temperature not specified in the publication
0.00047
V-11-023907
Homo sapiens
in 100 mM Tris-HCl pH 7.5, 100 mM KCl, 10 mM MgCl2, at 25°C
0.00002
(1S)-1-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-3-[2-[(oxan-4-yl)oxy]phenyl]-1-phenylpropan-1-ol
Homo sapiens
pH 7.0, 25°C, recombinant enzyme
0.000251
(4-methyl-1,4-diazepan-1-yl)(4'-((4-methyl-1,4-diazepan-1-yl)-methyl)-[1,1'-biphenyl]-4-yl)methanone
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.0528
1,1'-(benzene-1,3-diyldimethanediyl)bis(4-piperidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.0528 mM
0.0842
1,1'-(benzene-1,3-diyldimethanediyl)bis(4-pyrrolidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.0842 mM
0.0084
1,1'-(benzene-1,3-diyldimethanediyl)bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0084 mM
0.0072
1,1'-(benzene-1,3-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0072 mM
0.0375
1,1'-(benzene-1,3-diyldimethanediyl)bis[4-[(phenylamino)methyl]pyridinium] dibromide
Homo sapiens
-
IC50: 0.0375 mM
0.0377
1,1'-(benzene-1,4-diyldimethanediyl)bis(4-piperidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.0377 mM
0.024
1,1'-(benzene-1,4-diyldimethanediyl)bis(4-pyrrolidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.024 mM
0.0097
1,1'-(benzene-1,4-diyldimethanediyl)bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0097 mM
0.0029
1,1'-(benzene-1,4-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0029 mM
0.015
1,1'-(benzene-1,4-diyldimethanediyl)bis[4-[(phenylamino)methyl]pyridinium] dibromide
Homo sapiens
-
IC50: 0.015 mM
0.0119
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-amino-3-methylquinolinium) dibromide
Homo sapiens
-
IC50: 0.0119 mM
0.0206
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-amino-7-chloroquinolinium) dibromide
Homo sapiens
-
IC50: 0.0206 mM
0.0012
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-aminoquinolinium) dibromide
Homo sapiens
-
IC50: 0.0012 mM
0.0005
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-azepan-1-ylquinolinium) dibromide
Homo sapiens
-
IC50: 0.0005 mM
0.0019
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-piperidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.0019 mM
0.0058
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-pyrrolidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.0058 mM
0.0026
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0026 mM
0.0015
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0015 mM
0.0021
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
Homo sapiens
-
IC50: 0.0021 mM
0.147
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(7-amino-4-[[(4-chlorophenyl)amino]methyl]-8-methylquinolinium) dibromide
Homo sapiens
-
IC50: 0.147 mM
0.0012
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(7-chloro-4-pyrrolidin-1-ylquinolinium) dibromide
Homo sapiens
-
IC50: 0.0012 mM
0.0057
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis(7-chloro-4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
Homo sapiens
-
IC50: 0.0057 mM
0.0044
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[4-(dimethylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.0044 mM
0.0013
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[4-(phenylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.0013 mM
0.00043
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[4-[(phenylamino)methyl]pyridinium] dibromide
Homo sapiens
-
IC50: 0.00043 mM
0.0004
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.0004 mM
0.0568
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[7-amino-8-methyl-4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.0568 mM
0.0096
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[7-chloro-4-(dimethylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.0096 mM
0.0031
1,1'-(biphenyl-3,3'-diyldimethanediyl)bis[7-chloro-4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.0031 mM
0.2
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-amino-3-methylquinolinium) dibromide
Homo sapiens
-
IC50: above 0.2 mM
0.0633
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-amino-7-chloroquinolinium) dibromide
Homo sapiens
-
IC50: 0.0633 mM
0.0811
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-aminoquinolinium) dibromide
Homo sapiens
-
IC50: 0.0811 mM
0.0022
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-azepan-1-ylquinolinium) dibromide
Homo sapiens
-
IC50: 0.0022 mM
0.0088
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-piperidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.0088 mM
0.0111
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-pyrrolidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.0111 mM
0.0034
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0034 mM
0.0018
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0018 mM
0.002
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
Homo sapiens
-
IC50: 0.002 mM
0.0461
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(7-amino-4-[[(4-chlorophenyl)amino]methyl]-8-methylquinolinium) dibromide
Homo sapiens
-
IC50: 0.0461 mM
0.0198
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(7-chloro-4-pyrrolidin-1-ylquinolinium) dibromide
Homo sapiens
-
IC50: 0.0198 mM
0.0114
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis(7-chloro-4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
Homo sapiens
-
IC50: 0.0114 mM
0.0397
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[4-(dimethylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.0397 mM
0.0178
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[4-(phenylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.0178 mM
0.0043
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[4-[(phenylamino)methyl]pyridinium] dibromide
Homo sapiens
-
IC50: 0.0043 mM
0.003
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.003 mM
0.0961
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[7-amino-8-methyl-4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.0961 mM
0.0206
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[7-chloro-4-(dimethylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.0206 mM
0.0114
1,1'-(biphenyl-4,4'-diyldimethanediyl)bis[7-chloro-4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.0114 mM
0.098
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-piperidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: 0.098 mM
0.1
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-pyrrolidin-1-ylpyridinium) dibromide
Homo sapiens
-
IC50: above 0.1 mM
0.0482 - 0.1
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
0.1
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis[4-[(phenylamino)methyl]pyridinium] dibromide
Homo sapiens
-
IC50: above 0.1 mM
0.2
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(4-amino-7-chloroquinolinium) dibromide
Homo sapiens
-
IC50: above 0.2 mM
0.08
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(4-aminoquinolinium) dibromide
Homo sapiens
-
IC50: 0.08 mM
0.006
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(4-azepan-1-ylquinolinium) dibromide
Homo sapiens
-
IC50: 0.006 mM
0.0048
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
Homo sapiens
-
IC50: 0.0048 mM
0.0575
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(7-amino-4-[[(4-chlorophenyl)amino]methyl]-8-methylquinolinium) dibromide
Homo sapiens
-
IC50: 0.0575 mM
0.001
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(7-chloro-4-pyrrolidin-1-ylquinolinium) dibromide
Homo sapiens
-
IC50: 0.001 mM
0.0057
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis(7-chloro-4-[[(4-chlorophenyl)amino]methyl]quinolinium) dibromide
Homo sapiens
-
IC50: 0.0057 mM
0.0102
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[4-(dimethylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.0102 mM
0.0023
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[4-(phenylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.0023 mM
0.0014
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.0014 mM
0.133
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[7-amino-8-methyl-4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.133 mM
0.009
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[7-chloro-4-(dimethylamino)quinolinium] dibromide
Homo sapiens
-
IC50: 0.009 mM
0.0035
1,1'-[ethane-1,2-diylbis(benzene-4,1-diylmethanediyl)]bis[7-chloro-4-[(phenylamino)methyl]quinolinium] dibromide
Homo sapiens
-
IC50: 0.0035 mM
0.00143
1-((4'-methoxy-[1,1'-biphenyl]-4-yl)methyl)-4-methyl-1,4-diazepane
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.00232
1-([4-[2-(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)ethyl]phenyl]methyl)-4-(dimethylamino)pyridin-1-ium bromide
Homo sapiens
pH and temperature not specified in the publication, recombinant ChoKalpha
0.01836
1-([4-[2-(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)ethyl]phenyl]methyl)-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
Homo sapiens
pH and temperature not specified in the publication, recombinant ChoKalpha
0.01883
1-([4-[4-(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)butyl]phenyl]methyl)-4-(dimethylamino)pyridin-1-ium bromide
Homo sapiens
pH and temperature not specified in the publication, recombinant ChoKalpha
0.05
1-([4-[4-(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)butyl]phenyl]methyl)-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
Homo sapiens
above, pH and temperature not specified in the publication, recombinant ChoKalpha
0.0013 - 0.0015
1-methyl-4-((4'-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-4-yl)-methyl)-1,4-diazepane
0.0026
1-methyl-4-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methyl)-1,4-diazepane
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.0026
1-methyl-4-(naphthalen-2-ylmethyl)-1,4-diazepane
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.0015
1-[(4'-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl][1,1'-biphenyl]-4-yl)methyl]-4-(dimethylamino)pyridin-1-ium bromide
Homo sapiens
pH and temperature not specified in the publication, recombinant ChoKalpha
0.05
1-[(4'-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl][1,1'-biphenyl]-4-yl)methyl]-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
Homo sapiens
above, pH and temperature not specified in the publication, recombinant ChoKalpha
0.0004
1-[(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)methyl]-4-(dimethylamino)pyridin-1-ium bromide
Homo sapiens
pH and temperature not specified in the publication, recombinant ChoKalpha
0.00791
1-[(4-[[6-(benzylsulfanyl)-9H-purin-9-yl]methyl]phenyl)methyl]-4-(pyrrolidin-1-yl)pyridin-1-ium bromide
Homo sapiens
pH and temperature not specified in the publication, recombinant ChoKalpha
0.087
1-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]methanamine
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.0107
1-[[4-(4-[4-[(6-amino-9H-purin-9-yl)methyl]phenyl]butyl)phenyl]methyl]-4-(dimethylamino)pyridin-1-ium bromide
Homo sapiens
pH and temperature not specified in the publication, recombinant ChoKalpha
0.0132
12,19-diaza-1,8-diazoniapentacyclo[18.2.2.23,6.28,11.214,17]triaconta-1(22),3,5,8,10,14,16,20,23,25,27,29-dodecaene dibromide
Homo sapiens
-
IC50: 0.0132 mM
0.0021
12,21-diaza-1,8-diazoniapentacyclo[20.2.2.23,6.28,11.014,19]triaconta-1(24),3,5,8,10,14,16,18,22,25,27,29-dodecaene dibromide
Homo sapiens
-
IC50: 0.0021 mM
0.0003
14,21-diaza-1,10-diazoniapentacyclo[20.2.2.210,13.216,19.03,8]triaconta-1(24),3,5,7,10,12,16,18,22,25,27,29-dodecaene dibromide
0.000085
2'-fluoro-4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.000233
4,4'-((2,3-difluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis-(1-methyl-1,4-diazepane)
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.000165
4,4'-((2-fluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis(1-methyl-1,4-diazepane)
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.000255
4,4'-((3,5-difluoro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis-(1-methyl-1,4-diazepane)
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.000268
4,4'-((3-chloro-[1,1'-biphenyl]-4,4'-diyl)bis(methylene))bis(1-methyl-1,4-diazepane)
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.000457
4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-1,1'-biphenyl
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.000066
4,4'-bis((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.0248
5,10,11,16,17,22-hexahydro-6,9:18,21-diethenodibenzo[g,p][1,5,10,14]tetraazacyclooctadecine-6,21-diium dibromide
Homo sapiens
-
IC50: 0.0248 mM
0.0172
6-[(1-methyl-1,4-diazepan-6-yl)methyl]quinoline
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.0039
7-((4-methyl-1,4-diazepan-1-yl)methyl)quinolone
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.00495
methyl 4'-((4-methyl-1,4-diazepan-1-yl)methyl)-[1,1'-biphenyl]-4-carboxylate
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
2
[4-(4-methyl-1,4-diazepan-1-yl)phenyl]methanol
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
additional information
additional information
Homo sapiens
IC50 values for inhibitors with HepG2 cell and the cytosolic fraction of HepG2 cells, overview
-
0.0482
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: 0.0482 mM
0.1
1,1'-[(1S,2S)-cyclopropane-1,2-diyldiethane-2,1-diyl]bis(4-[[(3,5-dichlorophenyl)amino]methyl]pyridinium) dibromide
Homo sapiens
-
IC50: above 0.1 mM
0.0013
1-methyl-4-((4'-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-4-yl)-methyl)-1,4-diazepane
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.0015
1-methyl-4-((4'-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-4-yl)-methyl)-1,4-diazepane
Homo sapiens
pH 7.5, 25°C, recombinant enzyme
0.0003
14,21-diaza-1,10-diazoniapentacyclo[20.2.2.210,13.216,19.03,8]triaconta-1(24),3,5,7,10,12,16,18,22,25,27,29-dodecaene dibromide
Homo sapiens
-
IC50: 0.0003 mM
0.0003
14,21-diaza-1,10-diazoniapentacyclo[20.2.2.210,13.216,19.03,8]triaconta-1(24),3,5,7,10,12,16,18,22,25,27,29-dodecaene dibromide
Homo sapiens
-
IC50: 0.0003 mM, most potent inhibitor
0.0005 - 0.072
MN58b
Homo sapiens
-
specific inhibitor, IC50: 0.0005-0.072 mM depending on cell type
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000484
-
in 40 mM Tris/HCl with 10 mM MgCl2, 2 mM ATP and 0.25 mM choline, pH 7.4, at 37°C
additional information
additional information
-
exponentially growing cells: 484.04 pmol/mg/min (activity is determined after homogenizing a cell pellet in Tris/HCl buffer. Homogenisate of exponentially growing and confluent cells is centrifugated. Assay mixture containing 40 mM Tris/HCl with unlabelled carrier of 0.25 mM choline, (methyl-3H)choline (37 kBq/sample), 2 mM ATP and 10 mM MgCl2 were added to homogenate protein. After incubation, reaction is stopped by addition of ice-cold mixture of methanol and chloroform and lipid-metabolite extraction is then carried out. Protein content is set for each sample and total radioactivity is determined. Separation of (methyl-3H)-phosphocholine and (methyl-3H)-choline is carried out using ion exchange chromatography)
additional information
-
Genes significantly down-regulated by choline kinase: BCL2-interacting killer (apoptosis-inducing), stabilization of the calcium channel, cyclin G2. Inhibition of cell proliferation, T-cell surface protein tactile, cyclin-dependent kinase inhibitor 1A (p21, Cip1), cyclin-dependent kinase inhibitor 1B (p27, Kip1), dual-specificity-(Y)-tyrosine phosphor regulated kinase, Mad signalling (altered response to quimiotherapy), opioid receptor, mu 1 (negative regulat of cell proliferation), retinoblastoma-like 1 (p107) (Rb associated protein), transforming growth factor, beta receptor I, Toll like receptor (antitumoral immunity), immune escape of human cancer, Visinin like 1
additional information
-
increase in mRNA levels results in an increase in protein expression and ChoK enzymatic activity
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
Transfection of human HeK293T is carried out by the calcium phosphate method. The amount of plasmidic DNA is kept constant at 2 microg with the corresponding empty vector. Tumors induced by ChoK alpha over-expression in Hek293T are removed from the mice to generate the ChoK tumoral cell line ADJ. Different slices of the tissue are placed into culture 100mm dishes and treated with trypsin and 1 mg/ml of G418 to avoid murine cells contamination. The resultant cell line ADJ displays constitutive ChoK alpha activation and a fully transformed phenotype
ChoKalpha1 is upregulated in many tumor types, including breast, lung, colorectal, and prostate cancers
-
cancer tissue, frozen tissue samples are homogenised and lysed in buffer that contained 1.5 mmol/l magnesium chloride, 0.2 mmol/l EDTA, 0.3 M sodium chloride, 25 mmol/l HEPES at pH 7.5, 20 mmol/l beta-glycerophosphate, and 0.1% Triton X-100. Cells are lysed in ice-cold lysis buffer. Nuclei and detergent-insoluble material are removed by centrifugation.
-
HMEC cell line, a spontaneously immortalized nonmalignant mammary epithelial cell line
-
estrogen receptor-positive poorly metastatic breast cancer cell line
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
nuclear localization probability of 60.9% is detected for isoform CKalpha2 and of 52.2% for CKalpha1
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
choline kinase exists as two isoforms, alpha (ChoKalpha1 and 2) and beta. The alpha and beta isoforms are structurally similar and have sequence identity of 59%. The alpha isoform has a longer N-terminal sequence that shares no identity with the beta isoform, it also has a splice variant where residues 155-172 are missing (denoted ChoKalpha2), the unspliced variant, ChoKalpha1, has 457 residues
malfunction
physiological function
evolution
the mammalian choline kinase family is encoded by two distinct genes, ChoKalpha and ChoKbeta, resulting in three different isoforms, namely, ChoKalpha1, ChoKalpha2, and ChoKbeta. ChoKalpha1 (457 amino acids) and ChoKalpha2 (439 amino acids) are derived from a single gene (ChoKalpha) by alternative splicing
malfunction
-
silencing of CKalpha leads to a lethal phenotype with aberrant mitotic arrest and subsequent apoptosis, and is rescued by simultaneous knockdown of CKalpha and CKbeta isoforms
physiological function
additional information
malfunction
enzyme knockdown in MCF-7 and MCF-10A cells reduces epidermal growth factor-dependent cell proliferation
malfunction
the silencing of choline kinase alpha reduces cell proliferation. Moreover, pharmacological inhibition of choline kinase activity impairs the mineralization capacity of MG-63 cells
malfunction
increased cellular pCho levels lead to increased cellular proliferation. Other downstream products of the Kennedy pathway include phosphatidylcholine, which stimulates growth factor-induced DNA synthesis, and glycerophosphocholine, which is incorporated into cell membranes and is necessary for cell proliferation
physiological function
the enzyme is required for maximum epidermal growth factor-dependent cell growth in mammary epithelium-derived cell lines MCF-7 and MCF-10A
physiological function
choline kinase and its product phosphocholine are required for the normal growth and mineralization of MG-63 cells
physiological function
choline kinase alpha (ChoKalpha) is an enzyme that is upregulated in many types of cancer and has been shown to be tumorigenic
physiological function
choline kinase is linked to cancer malignancy and poor patient prognosis. It is the first enzyme in the Kennedy pathway, ultimately leading to the production of phosphatidylcholine, a key component of biological membranes. Choline kinase exists as two isoforms, alpha (ChoKalpha1 and 2) and beta. Choline kinase alpha also has a non-catalytic protein-binding role and a function in protein-protein interactions. Choline kinase alpha interacts with the SH3 domain of c-Src. This interaction is specific and is mediated by the poly-proline region found N-terminal to the catalytic domain of choline kinase, importance of ChoKalpha1 residues 49-79 for the interaction with the SH3 domain of c-Src. ChoKalpha1 may serve both scaffolding and signaling functions in the context of this oncogenic pathway. The interaction between ChoKalpha1 and the c-Src SH3 domain does not impact the choline kinase enzymatic activity, kinetic analysis, overview. Protein-protein interaction has no influence on enzymatic activity per se
physiological function
-
levels of CKalpa and CKbeta play an essential role in progression through mitosis, but not in resting cells or during DNA replication
physiological function
choline kinase beta, in concert with choline kinase alpha, and depending on its phosphorylation status, plays a critical role in carcinogenesis
physiological function
choline kinase (ChoK) is a cytosolic enzyme that catalyzes the MgATP-dependent phosphorylation of choline to phosphocholine (pCho) as the first step in the Kennedy pathway toward synthesis of the major membrane phospholipid, phosphatidylcholine (PtdCho)
additional information
ChoKALpha1DELTA49 binding to c-Src-SH3 requires an intact polyproline sequence preceding PL repeats motif but not ChoK kinase activity, two-state induced-fit model, binding analysis with ligand VSL12 (PDB ID 1QWF), overview
additional information
-
ChoKALpha1DELTA49 binding to c-Src-SH3 requires an intact polyproline sequence preceding PL repeats motif but not ChoK kinase activity, two-state induced-fit model, binding analysis with ligand VSL12 (PDB ID 1QWF), overview
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). CHKA_HUMAN
457
0
52249
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
52000
45000
52000
52000
-
2 * 52000, glioblastoma enzyme, alpha subtype, homo- or heterodimers formed from alpha and beta subtype
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
dimer
-
2 * 52000, glioblastoma enzyme, alpha subtype, homo- or heterodimers formed from alpha and beta subtype
homodimer
homodimer
ChoKalpha1 forms a functional dimer, crystal structure analysis
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with inhibitor V-11-023907, hanging drop vapor diffusion method, using 0.1 M Bis-Tris (pH 6.5), 25% (w/v) polyethylene glycol 3350, and 0.1 M MgCl2
in complex with inhibitors, hanging drop vapor diffusion method, using 10-30% (w/v) polyethylene glycol 5000 monomethyl ether and 0.2 M magnesium phormate
isoform ChoKalpha1 in complex with hemicholinium-3 and ADP, sitting drop vapor diffusion method, using 0.1 M HEPES (pH 7.5), 25% (w/v) polyethylene glycol 3350, and 0.2 M lithium sulfate
purified choline kinase catalytic domain of the protein, residues 80-457, and of SH3-ChoKalpha1(60-69) fusion protein, from 0.2 M zinc acetate, 0.1 M imidazole pH 8.0, and 20% w/v PEG 3000, drops of 0.002 ml protein at 10 mg/ml are set at a 1:1 ratio with reservoir solution, 2-3 weeks, X-ray diffraction structure determination and analysis at 1.5 A resolution, structure modeling using the structure of c-Src-SH3 with the NS5A peptide, PDB ID 4QT7, as a model
purified recombinant isozyme ChoKalpha truncated mutant DELTA79 in apoform and in complex with inhibitor TCD-717, sitting drop vapor diffusion method, mixing of 0.002 ml of 10 mg/ml protein solution with 0.002 ml of reservoir solution containing 0.1 M MES, pH 6.5, and 20% PEG 3350, 2-3 days, 20°C, crystals are soaked with TCD-717 by mixing a 50 mM solution of 100% DMSO-resuspended compound in a 1:4 ratio with the reservoir buffer, X-ray diffraction structure determination and analysis at 2.35 A resolution
sitting drop vapor diffusion method, using 20% (w/v) polyethylene glycol 3350 and 0.25 M potassium isothiocyanate
sitting drop vapour diffusion using 25 mM Tris/HCl (pH 7.5), 25 mM KCl, 0.5 mM dithiothreitol, 0.0005 ml of 0.1 M MgCl2 in 12-20% PEG 3350 with 0.2 M NaF
isoform ChoKbeta in complex with hemicholinium-3 and ADP, sitting drop vapor diffusion method, using 0.1 M sodium cacodylate (pH 6.5), 30% polyethylene glycol 4000, and 0.2 M ammonium sulfate
purified recombinant tagged enzyme in apoform and in complex with inhibitor 1-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]methanamine, mixing of 30 mg/ml protein solution with 0.1 M sodium formate, 8-12% PEG 3350 at 18°C, complex structures are obtained by soaking the inhibitors into the ChoKalpha1 crystals at a final concentration of 2-5 mM for 45-60 min before freezing in liquid nitrogen, X-ray diffraction structrue determination and analysis, modelling
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D306A
L401A
the mutant of isoform ChoKalpha1 exhibts a lower turnover number compared to the wild type enzyme
L401F
the mutant of isoform ChoKalpha1 exhibts a lower turnover number compared to the wild type enzyme
Y197/333F
the mutant shows reduced activity in the presence of epidermal growth factor receptor compared to the wild type enzyme
Y197F
the mutant shows reduced activity in the presence of epidermal growth factor receptor compared to the wild type enzyme
Y333F
the mutant shows reduced activity in the presence of epidermal growth factor receptor compared to the wild type enzyme
E125A
F352A
the mutant exhibits a higher turnover number compared to the wild type enzyme
F352L
the mutant exhibits a higher turnover number compared to the wild type enzyme
S39D/S40D
the choline kinase beta phosphorylation mimic behaves kinetically like the wild type enzyme
additional information
E125A
-
modest change in kcat/Km with a marked decrease in the affinity for Ca2+ and a significant increase in Km for Mg2+
additional information
comparison of the c-Src binding potential of ChoK as the full-length (FL) enzyme or with the first 49 (DELTA49) or 79 (DELTA79) residues truncated. The FL and DELTA49 variants include the poly-proline region, whereas the DELTA79 variant does not. All constructs extend up to the C-terminal residue, Val457, overview. The c-Src-ChoKalpha1 interaction occurs with the enzymatically dead D306A variant of ChoKalphaDELTA49, indicating that the association is independent of ChoKalpha1 activity. Both the P61A/P62A and the DELTA62 are difficult to purify and less soluble than their FL, DELTA49, or DELTA79 counterparts, as well as the P59A/P60A or P72A/P73A constructs
additional information
-
comparison of the c-Src binding potential of ChoK as the full-length (FL) enzyme or with the first 49 (DELTA49) or 79 (DELTA79) residues truncated. The FL and DELTA49 variants include the poly-proline region, whereas the DELTA79 variant does not. All constructs extend up to the C-terminal residue, Val457, overview. The c-Src-ChoKalpha1 interaction occurs with the enzymatically dead D306A variant of ChoKalphaDELTA49, indicating that the association is independent of ChoKalpha1 activity. Both the P61A/P62A and the DELTA62 are difficult to purify and less soluble than their FL, DELTA49, or DELTA79 counterparts, as well as the P59A/P60A or P72A/P73A constructs
additional information
construction of enzyme N-terminally truncated mutant ChoKalpha1-DELTA79, inhibitor TCD-717 binding structure, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
glutathione affinity column chromatography, Ni-NTA column chromatography, and Superdex 200 gel filtration
gluthatione-Sepharose column chromatography, Resource Q column chromatography and Superdex-200 gel filtration
recombinant His-SUMO-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta (DE3)pLysS by nickel affinity chromatography, and dialysis, if necessary the tag is cleaved, followd by another nickel affinity chromatography step, and dialysis, the last step for all is gel filtration
recombinant His-SUMO-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta (DE3)pLysS by nickel affinity chromatography, and dialysis, if necessary the tag is cleaved, followed by another nickel affinity chromatography step, and dialysis, the last step for all is gel filtration
recombinant tagged choline kinase alpha1 residues 75-457 by affinity and ion exchange chromatography, and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
gene CHKA, recombinant expression of His-SUMO-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta (DE3)pLysS
Small interfering RNA-chk (siRNA) is designed and transfected for 48 h using oligofectamine and Opti-MEM based on the observed decrease of Chk message using reverse transcription-PCR analysis within this time. Immunoblot assay results with Chk antibody shows significant reduction of Chk protein expression levels in MCF-12A, MCF-7, and MDA-MB-231 cells after transient siRNA-chk transfection.
-
The genomic sequence of the putative human chk-alpha promoter is obtained by performing a BLAST search in National Center for Biotechnology Information using the known promoter sequence of the rat chk-a gene as query sequence. A 2.3-kb region at the 5'-end of the human chk-a gene on chromosome 11, immediately upstream of the translation start site, is found to contain several putative HRE sites with the core sequence RCGTG. Due to its high GC content, this 2.3-kb region is cloned as four smaller overlapping fragments, and formamide (5%) is added in all PCRs. The four overlapping sequences are PCR amplified from human genomic DNA. The PCR products of paired sense and antisense primer sequences used for the cloning of these fragments (Chk) are subcloned into the pCR 2.1 TA vector. The full 2.3-kb promoter region is obtained by appropriate endonuclease digestions and ligation of these four overlapping fragments. Each of the four fragments alone, as well as several subligations of two or three consecutive fragments, and the full-length 2.3-kb chk-a promoter are cloned into the pGL4-basic Luc reporter vector.
-
Transfection of human HeK293T is carried out by the calcium phosphate method. The amount of plasmidic DNA is kept constant at 0.2 mg with the corresponding empty vector. Tumors induced by ChoK alpha over-expression in Hek293T are removed from the mice to generate the ChoK tumoral cell line ADJ. Different slices of the tissue are placed into culture 100mm dishes and treated with trypsin and G418 to avoid murine cells contamination. The resultant cell line (ADJ) displays constitutive ChoK alpha activation and a fully transformed phenotype
-
gene CHKA, recombinant expression of His-SUMO-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta (DE3)pLysS
gene CHKA, recombinant expression of His-SUMO-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta (DE3)pLysS
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
choline kinase activity and expression in MG-63 cells are significantly higher than those in primary human osteoblasts
expression levels increase with increasing malignancy of the cell lines, i.e., MDA-MB-231 > MCF-7 > MCF-12A
-
hypoxia decrease choline kinase activity and isoform ChKalpha mRNA and protein levels
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
choline kinase is a promising target for development of inhibitors and inhibition of tumor growth
medicine
diagnostics
drug development
medicine
medicine
the enzyme is implicated in tumorigenesis and an attractive target for anticancer chemotherapy
diagnostics
-
choline kinase alpha expression is a new prognostic factor that could be used to help identify patients with earlystage non-small-cell lung cancer who might be at high risk of recurrence, and to identify patients with favourable prognosis who could receive less aggressive treatment options or avoid adjuvant systemic treatment.
drug development
-
choline kinase is elevated in cancer cells and presents a novel target for increasing cell kill. Data support exploring transient Chk silencing as a broad-spectrum chemotherapeutic agent for cancer cells.
drug development
-
choline kinase is gaining importance as a potential target for anticancer therapy
drug development
-
target for therapy since its specific inhibitors display efficient antitumoral activity in vivo
medicine
potential target for anti-tumor drugs, potential use of the enzyme level as tumor marker
medicine
the enzyme is implicated in tumorigenesis and an attractive target for anticancer chemotherapy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hosaka, K.; Tanaka, S.; Nikawa, J.; Yamashita, S.
Cloning of a human choline kinase cDNA by complementation of the yeast cki mutation
FEBS Lett.
304
229-232
1992
Homo sapiens
Hernandez-Alcoceba, R.; Fernandez, F.; Lacal, J.C.
In vivo antitumor activity of choline kinase inhibitors: a novel target for anticancer drug discovery
Cancer Res.
59
3112-3118
1999
Homo sapiens
Ishidate, K.
Choline/ethanolamine kinase from mammalian tissues
Biochim. Biophys. Acta
1348
70-78
1997
Homo sapiens, Rattus norvegicus
Rodriguez-Gonzalez, A.; Ramirez de Molina, A.; Benitez-Rajal, J.; Lacal, J.C.
Phospholipase D and choline kinase: their role in cancer development and their potential as drug targets
Prog. Cell Cycle Res.
5
191-201
2003
Mus musculus (Q54AG5), Homo sapiens (Q9Y259)
Aoyama, C.; Liao, H.; Ishidate, K.
Structure and function of choline kinase isoforms in mammalian cells
Prog. Lipid Res.
43
266-281
2004
Saccharomyces cerevisiae, Caenorhabditis elegans, Homo sapiens, Mus musculus, Rattus norvegicus
Al-Saeedi, F.; Smith, T.; Welch, A.
[Methyl-3H]-choline incorporation into MCF-7 cells: correlation with proliferation, choline kinase and phospholipase D assay
Anticancer Res.
27
901-906
2007
Homo sapiens
Glunde, K.; Raman, V.; Mori, N.; Bhujwalla, Z.M.
RNA interference-mediated choline kinase suppression in breast cancer cells induces differentiation and reduces proliferation
Cancer Res.
65
11034-11043
2005
Homo sapiens
Milanese, L.; Espinosa, A.; Campos, J.M.; Gallo, M.A.; Entrena, A.
Insight into the inhibition of human choline kinase: homology modeling and molecular dynamics simulations
ChemMedChem
1
1216-1228
2006
Caenorhabditis elegans, Homo sapiens
Janardhan, S.; Srivani, P.; Sastry, G.N.
Choline kinase: an important target for cancer
Curr. Med. Chem.
13
1169-1186
2006
Saccharomyces cerevisiae, Caenorhabditis elegans, Homo sapiens, Mus musculus, Rattus norvegicus, Schizosaccharomyces pombe
Campos, J.M.; Sanchez-Martin, R.M.; Conejo-Garcia, A.; Entrena, A.; Gallo, M.A.; Espinosa, A.
(Q)SAR studies to design new human choline kinase inhibitors as antiproliferative drugs
Curr. Med. Chem.
13
1231-1248
2006
Homo sapiens
Conejo-Garcia, A.; Entrena, A.; Campos, J.M.; Sanchez-Martin, R.M.; Gallo, M.A.; Espinosa, A.
Towards a model for the inhibition of choline kinase by a new type of inhibitor
Eur. J. Med. Chem.
40
315-319
2005
Homo sapiens
Rodriguez-Gonzalez, A.; Ramirez de Molina, A.; Banez-Coronel, M.; Megias, D.; Lacal, J.C.
Inhibition of choline kinase renders a highly selective cytotoxic effect in tumour cells through a mitochondrial independent mechanism
Int. J. Oncol.
26
999-1008
2005
Homo sapiens
Malito, E.; Sekulic, N.; Too, W.C.; Konrad, M.; Lavie, A.
Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine
J. Mol. Biol.
364
136-151
2006
Homo sapiens (P35790), Homo sapiens
Mori, N.; Glunde, K.; Takagi, T.; Raman, V.; Bhujwalla, Z.M.
Choline kinase down-regulation increases the effect of 5-fluorouracil in breast cancer cells
Cancer Res.
67
11284-11290
2007
Homo sapiens
Glunde, K.; Shah, T.; Winnard, P.T.; Raman, V.; Takagi, T.; Vesuna, F.; Artemov, D.; Bhujwalla, Z.M.
Hypoxia regulates choline kinase expression through hypoxia-inducible factor-1 alpha signaling in a human prostate cancer model
Cancer Res.
68
172-180
2008
Homo sapiens
Ramirez de Molina, A.; Gallego-Ortega, D.; Sarmentero-Estrada, J.; Lagares, D.; Gomez Del Pulgar, T.; Bandres, E.; Garcia-Foncillas, J.; Lacal, J.C.
Choline kinase as a link connecting phospholipid metabolism and cell cycle regulation: implications in cancer therapy
Int. J. Biochem. Cell Biol.
40
1753-1763
2008
Homo sapiens
Ramirez de Molina, A.; Sarmentero-Estrada, J.; Belda-Iniesta, C.; Taron, M.; Ramirez de Molina, V.; Cejas, P.; Skrzypski, M.; Gallego-Ortega, D.; de Castro, J.; Casado, E.; Garcia-Cabezas, M.A.; Sanchez, J.J.; Nistal, M.; Rosell, R.; Gonzalez-Baron, M.; Lacal, J.C.
Expression of choline kinase alpha to predict outcome in patients with early-stage non-small-cell lung cancer: a retrospective study
Lancet Oncol.
8
889-897
2007
Homo sapiens
Srivani, P.; Sastry, G.N.
Potential choline kinase inhibitors: a molecular modeling study of bis-quinolinium compounds
J. Mol. Graph. Model.
27
676-688
2009
Homo sapiens (P35790)
Ross, J.; Najjar, A.M.; Sankaranarayanapillai, M.; Tong, W.P.; Kaluarachchi, K.; Ronen, S.M.
Fatty acid synthase inhibition results in a magnetic resonance-detectable drop in phosphocholine
Mol. Cancer Ther.
7
2556-2565
2008
Homo sapiens
Chua, B.T.; Gallego-Ortega, D.; Ramirez de Molina, A.; Ullrich, A.; Lacal, J.C.; Downward, J.
Regulation of Akt(ser473)phosphorylation by Choline kinase in breast carcinoma cells
Mol. Cancer
8
131
2009
Homo sapiens
Nimmagadda, S.; Glunde, K.; Pomper, M.G.; Bhujwalla, Z.M.
Pharmacodynamic markers for choline kinase down-regulation in breast cancer cells
Neoplasia
11
477-484
2009
Homo sapiens
Yalcin, A.; Clem, B.; Makoni, S.; Clem, A.; Nelson, K.; Thornburg, J.; Siow, D.; Lane, A.N.; Brock, S.E.; Goswami, U.; Eaton, J.W.; Telang, S.; Chesney, J.
Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling
Oncogene
29
139-149
2009
Homo sapiens
Gallego-Ortega, D.; Ramirez de Molina, A.; Ramos, M.A.; Valdes-Mora, F.; Barderas, M.G.; Sarmentero-Estrada, J.; Lacal, J.C.
Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment
PLoS ONE
4
e7819
2009
Homo sapiens (P35790), Homo sapiens (Q9Y259), Homo sapiens
Hudson, C.S.; Knegtel, R.M.; Brown, K.; Charlton, P.A.; Pollard, J.R.
Kinetic and mechanistic characterisation of choline kinase-alpha
Biochim. Biophys. Acta
1834
1107-1116
2013
Homo sapiens (P35790), Homo sapiens
Rubio-Ruiz, B.; Conejo-Garcia, A.; Rios-Marco, P.; Carrasco-Jimenez, M.P.; Segovia, J.; Marco, C.; Gallo, M.A.; Espinosa, A.; Entrena, A.
Design, synthesis, theoretical calculations and biological evaluation of new non-symmetrical choline kinase inhibitors
Eur. J. Med. Chem.
50
154-162
2012
Homo sapiens (P35790)
Gruber, J.; See Too, W.C.; Wong, M.T.; Lavie, A.; McSorley, T.; Konrad, M.
Balance of human choline kinase isoforms is critical for cell cycle regulation: implications for the development of choline kinase-targeted cancer therapy
FEBS J.
279
1915-1928
2012
Homo sapiens
Hong, B.S.; Allali-Hassani, A.; Tempel, W.; Finerty, P.J.; Mackenzie, F.; Dimov, S.; Vedadi, M.; Park, H.W.
Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: single amino acid near the active site influences inhibitor sensitivity
J. Biol. Chem.
285
16330-16340
2010
Homo sapiens (P35790), Homo sapiens (Q9Y259), Homo sapiens
Bansal, A.; Harris, R.A.; DeGrado, T.R.
Choline phosphorylation and regulation of transcription of choline kinase alpha in hypoxia
J. Lipid Res.
53
149-157
2012
Homo sapiens
Miyake, T.; Parsons, S.J.
Functional interactions between choline kinase alpha, epidermal growth factor receptor and c-Src in breast cancer cell proliferation
Oncogene
31
1431-1441
2012
Homo sapiens (P35790)
Li, Z.; Wu, G.; van der Veen, J.N.; Hermansson, M.; Vance, D.E.
Phosphatidylcholine metabolism and choline kinase in human osteoblasts
Biochim. Biophys. Acta
1841
859-867
2014
Homo sapiens (P35790), Homo sapiens
Schiaffino-Ortega, S.; Lopez-Cara, L.C.; Rios-Marco, P.; Carrasco-Jimenez, M.P.; Gallo, M.A.; Espinosa, A.; Marco, C.; Entrena, A.
New non-symmetrical choline kinase inhibitors
Bioorg. Med. Chem.
21
7146-7154
2013
Homo sapiens (P35790)
Rubio-Ruiz, B.; Figuerola-Conchas, A.; Ramos-Torrecillas, J.; Capitan-Canadas, F.; Rios-Marco, P.; Carrasco, M.P.; Gallo, M.A.; Espinosa, A.; Marco, C.; Ruiz, C.; Entrena, A.; Hurtado-Guerrero, R.; Conejo-Garcia, A.
Discovery of a new binding site on human choline kinase alpha1: design, synthesis, crystallographic studies, and biological evaluation of asymmetrical bispyridinium derivatives
J. Med. Chem.
57
507-515
2014
Homo sapiens (P35790), Homo sapiens
Zech, S.G.; Kohlmann, A.; Zhou, T.; Li, F.; Squillace, R.M.; Parillon, L.E.; Greenfield, M.T.; Miller, D.P.; Qi, J.; Thomas, R.M.; Wang, Y.; Xu, Y.; Miret, J.J.; Shakespeare, W.C.; Zhu, X.; Dalgarno, D.C.
Novel small molecule inhibitors of choline kinase identified by fragment-based drug discovery
J. Med. Chem.
59
671-686
2016
Homo sapiens (P35790), Homo sapiens
Trousil, S.; Carroll, L.; Kalusa, A.; Aberg, O.; Kaliszczak, M.; Aboagye, E.O.
Design of symmetrical and nonsymmetrical N,N-dimethylaminopyridine derivatives as highly potent choline kinase alpha inhibitors
MedChemComm
2013
693-696
2013
Homo sapiens
Mori, N.; Gadiya, M.; Wildes, F.; Krishnamachary, B.; Glunde, K.; Bhujwalla, Z.M.
Characterization of choline kinase in human endothelial cells
NMR Biomed.
26
1501-1507
2013
Homo sapiens (P35790), Homo sapiens
Chang, C.C.; Few, L.L.; Konrad, M.; See Too, W.C.
Phosphorylation of human choline kinase beta by protein kinase A: its impact on activity and inhibition
PLoS ONE
11
e0154702
2016
Homo sapiens (Q9Y259), Homo sapiens
Schiaffino-Ortega, S.; Baglioni, E.; Mariotto, E.; Bortolozzi, R.; Serran-Aguilera, L.; Rios-Marco, P.; Carrasco-Jimenez, M.P.; Gallo, M.A.; Hurtado-Guerrero, R.; Marco, C.; Basso, G.; Viola, G.; Entrena, A.; Lopez-Cara, L.C.
Design, synthesis, crystallization and biological evaluation of new symmetrical biscationic compounds as selective inhibitors of human choline kinase alpha1 (ChoKalpha1)
Sci. Rep.
6
23793
2016
Homo sapiens (P35790), Homo sapiens
Kall, S.L.; Delikatny, E.J.; Lavie, A.
Identification of a unique inhibitor-binding site on choline kinase alpha
Biochemistry
57
1316-1325
2018
Homo sapiens (P35790)
Zech, S.; Kohlmann, A.; Zhou, T.; Li, F.; Squillace, R.; Parillon, L.; Greenfield, M.; Miller, D.; Qi, J.; Thomas, R.; Wang, Y.; Xu, Y.; Miret, J.; Shakespeare, W.; Zhu, X.; Dalgarno, D.
Novel small molecule inhibitors of choline kinase identified by fragment-based drug discovery
J. Med. Chem.
59
671-686
2016
Homo sapiens (O54804), Homo sapiens
Rubio-Ruiz, B.; Rixados-Marco, P.; Carrasco-Jimenez, M.; Espinosa, A.; Hurtado-Guerrero, R.; Marco, C.; Conejo-Garcixada, A.; Entrena, A.
Choline kinase inhibition and docking studies of a series of 6-(benzylthio)-9H-purin-9-yl-pyridinium derivatives
Med. Chem. Res.
26
2809-2815
2017
Homo sapiens (O54804)
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