BRENDA - Enzyme Database show

Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors

Jessop, T.C.; Tarver, J.E.; Carlsen, M.; Xu, A.; Healy, J.P.; Heim-Riether, A.; Fu, Q.; Taylor, J.A.; Augeri, D.J.; Shen, M.; Stouch, T.R.; Swanson, R.V.; Tari, L.W.; Hunter, M.; Hoffman, I.; Keyes, P.E.; Yu, X.C.; Miranda, M.; Liu, Q.; Swaffield, J.C.; David Kimball, S.; Nouraldeen, A.; Wilson, A.G.; Foushee, A.M.; Bioorg. Med. Chem. Lett. 19, 6784-6787 (2009)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
2.7.1.74
3'-[[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]sulfamoyl]biphenyl-4-carboxamide
-
Homo sapiens
2.7.1.74
4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine
-
Homo sapiens
2.7.1.74
5-Fluoro-2'-deoxycytidine
competitive inhibitor
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2',4'-dichlorobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2'-chlorobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-carboxamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-carboxamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-(methylsulfonyl)biphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-chlorobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-cyanobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-formylbiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methylbiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-(1-benzothiophen-2-yl)pyridine-2-carboxamide
potent, selective, and orally bioavailable inhibitor of dCK
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-bromobenzenesulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-nitrobenzenesulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]benzenesulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-carboxamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-sulfonamide
-
Homo sapiens
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.7.1.74
Homo sapiens
P27707
-
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.7.1.74
ATP + 2'-deoxycytidine
-
702604
Homo sapiens
ADP + 2'-deoxycytidine 5'-phosphate
-
-
-
?
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
2.7.1.74
ATP
-
Homo sapiens
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.7.1.74
0.0000017
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-(1-benzothiophen-2-yl)pyridine-2-carboxamide
2.7.1.74
0.000021
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2',4'-dichlorobiphenyl-3-sulfonamide
2.7.1.74
0.000021
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-carboxamide
2.7.1.74
0.000021
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-sulfonamide
2.7.1.74
0.000023
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-carboxamide
2.7.1.74
0.00003
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
2.7.1.74
0.000042
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
2.7.1.74
0.000045
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2'-chlorobiphenyl-3-sulfonamide
2.7.1.74
0.000049
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-cyanobiphenyl-3-sulfonamide
2.7.1.74
0.000051
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-chlorobiphenyl-3-sulfonamide
2.7.1.74
0.000063
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-(methylsulfonyl)biphenyl-3-sulfonamide
2.7.1.74
0.000064
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-sulfonamide
2.7.1.74
0.000079
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-sulfonamide
2.7.1.74
0.000089
-
-
Homo sapiens
3'-[[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]sulfamoyl]biphenyl-4-carboxamide
2.7.1.74
0.00011
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methylbiphenyl-3-sulfonamide
2.7.1.74
0.00012
-
-
Homo sapiens
5-Fluoro-2'-deoxycytidine
2.7.1.74
0.00012
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-sulfonamide
2.7.1.74
0.00026
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-carboxamide
2.7.1.74
0.00035
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
2.7.1.74
0.00051
-
-
Homo sapiens
4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine
2.7.1.74
0.0019
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
2.7.1.74
0.0027
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-bromobenzenesulfonamide
2.7.1.74
0.0032
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-nitrobenzenesulfonamide
2.7.1.74
0.0036
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]benzenesulfonamide
2.7.1.74
0.0153
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-formylbiphenyl-3-sulfonamide
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
2.7.1.74
ATP
-
Homo sapiens
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.7.1.74
0.0000017
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-(1-benzothiophen-2-yl)pyridine-2-carboxamide
2.7.1.74
0.000021
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2',4'-dichlorobiphenyl-3-sulfonamide
2.7.1.74
0.000021
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-carboxamide
2.7.1.74
0.000021
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-sulfonamide
2.7.1.74
0.000023
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-carboxamide
2.7.1.74
0.00003
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
2.7.1.74
0.000042
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
2.7.1.74
0.000045
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2'-chlorobiphenyl-3-sulfonamide
2.7.1.74
0.000049
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-cyanobiphenyl-3-sulfonamide
2.7.1.74
0.000051
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-chlorobiphenyl-3-sulfonamide
2.7.1.74
0.000063
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-(methylsulfonyl)biphenyl-3-sulfonamide
2.7.1.74
0.000064
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-sulfonamide
2.7.1.74
0.000079
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-sulfonamide
2.7.1.74
0.000089
-
-
Homo sapiens
3'-[[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]sulfamoyl]biphenyl-4-carboxamide
2.7.1.74
0.00011
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methylbiphenyl-3-sulfonamide
2.7.1.74
0.00012
-
-
Homo sapiens
5-Fluoro-2'-deoxycytidine
2.7.1.74
0.00012
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-sulfonamide
2.7.1.74
0.00026
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-carboxamide
2.7.1.74
0.00035
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
2.7.1.74
0.00051
-
-
Homo sapiens
4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine
2.7.1.74
0.0019
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
2.7.1.74
0.0027
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-bromobenzenesulfonamide
2.7.1.74
0.0032
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-nitrobenzenesulfonamide
2.7.1.74
0.0036
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]benzenesulfonamide
2.7.1.74
0.0153
-
-
Homo sapiens
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-formylbiphenyl-3-sulfonamide
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
2.7.1.74
3'-[[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]sulfamoyl]biphenyl-4-carboxamide
-
Homo sapiens
2.7.1.74
4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine
-
Homo sapiens
2.7.1.74
5-Fluoro-2'-deoxycytidine
competitive inhibitor
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2',4'-dichlorobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2'-chlorobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-carboxamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-carboxamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-(methylsulfonyl)biphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-chlorobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-cyanobiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-formylbiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methylbiphenyl-3-sulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-(1-benzothiophen-2-yl)pyridine-2-carboxamide
potent, selective, and orally bioavailable inhibitor of dCK
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-bromobenzenesulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-nitrobenzenesulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]benzenesulfonamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-carboxamide
-
Homo sapiens
2.7.1.74
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-sulfonamide
-
Homo sapiens
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.7.1.74
ATP + 2'-deoxycytidine
-
702604
Homo sapiens
ADP + 2'-deoxycytidine 5'-phosphate
-
-
-
?