BRENDA - Enzyme Database show

Development of new deoxycytidine kinase inhibitors and noninvasive in vivo evaluation using positron emission tomography

Murphy, J.M.; Armijo, A.L.; Nomme, J.; Lee, C.H.; Smith, Q.A.; Li, Z.; Campbell, D.O.; Liao, H.I.; Nathanson, D.A.; Austin, W.R.; Lee, J.T.; Darvish, R.; Wei, L.; Wang, J.; Su, Y.; Damoiseaux, R.; Sadeghi, S.; Phelps, M.E.; Herschman, H.R.; Czernin, J.; Alexandrova, A.N.; Jung, M.E.; Lavie, A.; Radu, C.G.; J. Med. Chem. 56, 6696-6708 (2013)

Data extracted from this reference:

Crystallization (Commentary)
EC Number
Crystallization
Organism
2.7.1.74
in complex with inhibitors 2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-methylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine and 1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)-2-methylpropan-2-ol , hanging drop vapor diffusion method, using 0.9-1.5 M trisodium citrate dehydrate and 25 mM HEPES (pH 7.5), at 12°C
Homo sapiens
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
2.7.1.74
1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)-2-methylpropan-2-ol
-
Homo sapiens
2.7.1.74
1-[5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]propan-2-ol
-
Homo sapiens
2.7.1.74
2,2'-[[4-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-1,2-phenylene]bis(oxy)]di(ethan-1-ol)
-
Homo sapiens
2.7.1.74
2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-methylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-propylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(3,5-difluorophenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(3-fluorophenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(3-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(4-ethoxy-3-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(4-fluorophenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine
-
Homo sapiens
2.7.1.74
2-([[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(4-methylphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(5-bromo-2-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[3-(2-fluoroethoxy)-4-(fluoromethoxy)phenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[3-(2-fluoroethoxy)-4-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[3-(2-fluoroethoxy)-4-methylphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[3-(3-fluoropropoxy)-4-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[4-(2-fluoroethoxy)-2-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[4-(2-fluoroethoxy)-3-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[4-ethoxy-3-(2-fluoroethoxy)phenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[5-(2-fluoroethoxy)-2-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[3-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-5-fluorophenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[3-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)phenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-fluorophenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[5-(4-[[(4-aminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[[(2-phenyl-1,3-thiazol-4-yl)methyl]sulfanyl]pyrimidine
-
Homo sapiens
2.7.1.74
3-[5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]propan-1-ol
-
Homo sapiens
2.7.1.74
5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenol
-
Homo sapiens
2.7.1.74
N-(2-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide
-
Homo sapiens
2.7.1.74
N-[2-[3-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-5-fluorophenoxy]ethyl]methanesulfonamide
-
Homo sapiens
2.7.1.74
N-[2-[3-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)phenoxy]ethyl]methanesulfonamide
-
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.7.1.74
ATP + deoxycytidine
Homo sapiens
-
ADP + dCMP
-
-
?
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 + 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine
-
738829
Homo sapiens
ADP + 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine 5'-phosphate
-
-
-
?
2.7.1.74
ATP + deoxycytidine
-
738829
Homo sapiens
ADP + dCMP
-
-
-
?
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
2.7.1.74
0.0000005
-
N-(2-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide
at pH 7.6 and 37°C
Homo sapiens
2.7.1.74
0.0000008
-
1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)-2-methylpropan-2-ol
at pH 7.6 and 37°C
Homo sapiens
2.7.1.74
0.0000015
-
2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-propylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
at pH 7.6 and 37°C
Homo sapiens
2.7.1.74
0.0000095
-
2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-methylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
at pH 7.6 and 37°C
Homo sapiens
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.7.1.74
0.00112
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(4-ethoxy-3-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.00167
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(3-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.00176
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(5-bromo-2-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.00202
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.00232
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(4-methylphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.1
-
IC50 above 0.1 mM, at pH 7.6 and 37°C
Homo sapiens
2-([[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine
2.7.1.74
0.1
-
IC50 above 0.1 mM, at pH 7.6 and 37°C
Homo sapiens
2-[[(2-phenyl-1,3-thiazol-4-yl)methyl]sulfanyl]pyrimidine
Crystallization (Commentary) (protein specific)
EC Number
Crystallization
Organism
2.7.1.74
in complex with inhibitors 2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-methylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine and 1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)-2-methylpropan-2-ol , hanging drop vapor diffusion method, using 0.9-1.5 M trisodium citrate dehydrate and 25 mM HEPES (pH 7.5), at 12°C
Homo sapiens
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.7.1.74
0.00112
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(4-ethoxy-3-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.00167
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(3-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.00176
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(5-bromo-2-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.00202
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.00232
-
at pH 7.6 and 37°C
Homo sapiens
2-([[2-(4-methylphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
2.7.1.74
0.1
-
IC50 above 0.1 mM, at pH 7.6 and 37°C
Homo sapiens
2-([[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine
2.7.1.74
0.1
-
IC50 above 0.1 mM, at pH 7.6 and 37°C
Homo sapiens
2-[[(2-phenyl-1,3-thiazol-4-yl)methyl]sulfanyl]pyrimidine
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
2.7.1.74
1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)-2-methylpropan-2-ol
-
Homo sapiens
2.7.1.74
1-[5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]propan-2-ol
-
Homo sapiens
2.7.1.74
2,2'-[[4-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-1,2-phenylene]bis(oxy)]di(ethan-1-ol)
-
Homo sapiens
2.7.1.74
2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-methylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-propylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(3,5-difluorophenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(3-fluorophenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(3-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(4-ethoxy-3-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(4-fluorophenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine
-
Homo sapiens
2.7.1.74
2-([[2-(4-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(4-methylphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-([[2-(5-bromo-2-methoxyphenyl)-1,3-thiazol-4-yl]methyl]sulfanyl)pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[3-(2-fluoroethoxy)-4-(fluoromethoxy)phenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[3-(2-fluoroethoxy)-4-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[3-(2-fluoroethoxy)-4-methylphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[3-(3-fluoropropoxy)-4-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[4-(2-fluoroethoxy)-2-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[4-(2-fluoroethoxy)-3-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[4-ethoxy-3-(2-fluoroethoxy)phenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[([2-[5-(2-fluoroethoxy)-2-methoxyphenyl]-1,3-thiazol-4-yl]methyl)sulfanyl]pyrimidine-4,6-diamine
-
Homo sapiens
2.7.1.74
2-[3-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-5-fluorophenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[3-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)phenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-fluorophenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[5-(4-[[(4-aminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]ethan-1-ol
-
Homo sapiens
2.7.1.74
2-[[(2-phenyl-1,3-thiazol-4-yl)methyl]sulfanyl]pyrimidine
-
Homo sapiens
2.7.1.74
3-[5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]propan-1-ol
-
Homo sapiens
2.7.1.74
5-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-2-methoxyphenol
-
Homo sapiens
2.7.1.74
N-(2-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide
-
Homo sapiens
2.7.1.74
N-[2-[3-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)-5-fluorophenoxy]ethyl]methanesulfonamide
-
Homo sapiens
2.7.1.74
N-[2-[3-(4-[[(4,6-diaminopyrimidin-2-yl)sulfanyl]methyl]-5-propyl-1,3-thiazol-2-yl)phenoxy]ethyl]methanesulfonamide
-
Homo sapiens
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
2.7.1.74
0.0000005
-
N-(2-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide
at pH 7.6 and 37°C
Homo sapiens
2.7.1.74
0.0000008
-
1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)-2-methylpropan-2-ol
at pH 7.6 and 37°C
Homo sapiens
2.7.1.74
0.0000015
-
2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-propylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
at pH 7.6 and 37°C
Homo sapiens
2.7.1.74
0.0000095
-
2-(((2-(3-(2-fluoroethoxy)-4-methoxyphenyl)-5-methylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
at pH 7.6 and 37°C
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.7.1.74
ATP + deoxycytidine
Homo sapiens
-
ADP + dCMP
-
-
?
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 + 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine
-
738829
Homo sapiens
ADP + 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine 5'-phosphate
-
-
-
?
2.7.1.74
ATP + deoxycytidine
-
738829
Homo sapiens
ADP + dCMP
-
-
-
?