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Literature summary for 2.7.1.48 extracted from

  • Okesli-Armlovich, A.; Gupta, A.; Jimenez, M.; Auld, D.; Liu, Q.; Bassik, M.C.; Khosla, C.
    Discovery of small molecule inhibitors of human uridine-cytidine kinase 2 by high-throughput screening (2019), Bioorg. Med. Chem. Lett., 29, 2559-2564 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.1.48

Cloned(Commentary)

Cloned (Comment) Organism
gene UCK2, recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(1E)-[[4-(4-tert-butylphenyl)-5-cyano-6-hydroxypyrimidin-2-yl]sulfanyl]-N-(2-methoxyphenyl)ethanimidic acid
-
 Homo sapiens
(1Z)-[([5-[(4-fluorophenyl)methyl]-7-oxo-6,7-dihydro-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]methyl)sulfanyl]-N-(2-methylphenyl)ethanimidic acid
-
 Homo sapiens
2-[(5-cyano-4-hydroxy-6-phenylpyrimidin-2-yl)sulfanyl]-N-(4-ethylphenyl)acetamide
-
 Homo sapiens
2-[[1-(4-fluorophenyl)-4-oxo-5H-pyrazolo[3,4-d]pyrimidin-6-yl]sulfanyl]-N-[2-(trifluoromethyl)phenyl]acetamide
-
 Homo sapiens
2-[[4-(4-tert-butylphenyl)-5-cyano-6-hydroxypyrimidin-2-yl]sulfanyl]-N-(4-chlorophenyl)acetamide
-
 Homo sapiens
3-(2-[[9-methoxy-2-(4-methylphenyl)-5H-[1]benzopyrano[2,3-d]pyrimidin-4-yl]sulfanyl]acetamido)benzoic acid
-
 Homo sapiens
3-(2-[[9-methyl-2-(4-methylphenyl)-5H-[1]benzopyrano[2,3-d]pyrimidin-4-yl]sulfanyl]acetamido)benzoic acid
-
 Homo sapiens
3-[[2-[[2-(4-fluorophenyl)-5H-chromeno[2,3-d]pyrimidin-4-yl]sulfanyl]acetyl]amino]benzoic acid
-
 Homo sapiens
4-(2-[[9-methyl-2-(4-methylphenyl)-5H-[1]benzopyrano[2,3-d]pyrimidin-4-yl]sulfanyl]acetamido)benzoic acid
-
 Homo sapiens
4-[[2-[[2-(4-methoxyphenyl)-5H-chromeno[2,3-d]pyrimidin-4-yl]sulfanyl]acetyl]amino]benzoic acid
-
 Homo sapiens
ATP noncompetitive Homo sapiens
ethanimidic acid
-
 Homo sapiens
additional information establishment and miniaturization of an in vitro assay for UCK2 activity and high-throughput screen against an about 40,000-compound library to generate drug-like leads. Analysis of the structures, activities, and modes of inhibition of the most promising hits, overview. Non-competitive UCK2 inhibitors are identified which are able to suppress nucleoside salvage in cells both in the presence and absence of dihydroorotate dehydrogenase (DHODH) inhibitors. No inhibition by 2-[[9-methyl-2-(4-methylphenyl)-5H-[1]benzopyrano[2,3-d]pyrimidin-4-yl]sulfanyl]-N-phenylacetamide, and (1Z)-N-(4-fluorophenyl)[([5-[(4-fluorophenyl)methyl]-7-oxo-6,7-dihydro-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]methyl)sulfanyl]ethanimidic acid Homo sapiens
N-(3,5-dimethylphenyl)-2-[([5-[(4-fluorophenyl)methyl]-7-oxo-2,5,6,7-tetrahydro-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]methyl)sulfanyl]acetamide inhibits 3'-ethynylcytidine 5'-triphosphate (5-EU) salvage by about 40% at 0.05 mM Homo sapiens
N-(4-bromophenyl)-2-[[1-(4-fluorophenyl)-4-hydroxy-1H-pyrazolo[3,4-d]pyrimidin-6-yl]sulfanyl]acetamide
-
 Homo sapiens
uridine noncompetitive Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.061
-
 uridine pH 8.5, temperature not specified in the publication Homo sapiens
0.062
-
 ATP pH 8.5, temperature not specified in the publication Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
 Homo sapiens 5829
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 3'-C-ethynylcytidine Homo sapiens i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine ADP + 3'-C-ethynylcytidine 5'-phosphate
-
 ir
ATP + 3'-C-ethynylcytidine 5'-diphosphate Homo sapiens
-
 ADP + 3'-C-ethynylcytidine 5'-triphosphate
-
 ?
ATP + 3'-C-ethynylcytidine 5'-phosphate Homo sapiens
-
 ADP + 3'-C-ethynylcytidine 5'-diphosphate
-
 ?
ATP + 3'-C-ethynyluridine Homo sapiens i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine ADP + 3'-C-ethynyluridine 5'-phosphate
-
 ?
ATP + 3'-C-ethynyluridine 5'-diphosphate Homo sapiens
-
 ADP + 3'-C-ethynyluridine 5'-triphosphate
-
 ?
ATP + 3'-C-ethynyluridine 5'-phosphate Homo sapiens
-
 ADP + 3'-C-ethynyluridine 5'-diphosphate
-
 ?
ATP + cytidine Homo sapiens
-
 ADP + CMP
-
 ?
ATP + uridine Homo sapiens
-
 ADP + UMP
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9BZX2
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant C-terminally His6-tagged enzyme from Escherichia coli by nickel affinity chromatography followed by ion-exchange chromatography Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell UCK2 is differentially expressed in many cancer tissues and in cells subjected to viral infection Homo sapiens
-
K-562 cell UCK2 is the predominant UCK isozyme expressed in K562 cells Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 3'-C-ethynylcytidine i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine Homo sapiens ADP + 3'-C-ethynylcytidine 5'-phosphate
-
 ir
ATP + 3'-C-ethynylcytidine 5'-diphosphate
-
 Homo sapiens ADP + 3'-C-ethynylcytidine 5'-triphosphate
-
 ?
ATP + 3'-C-ethynylcytidine 5'-phosphate
-
 Homo sapiens ADP + 3'-C-ethynylcytidine 5'-diphosphate
-
 ?
ATP + 3'-C-ethynyluridine i.e. 1-(3-C-ethynyl-beta-D-ribopentofuranosyl)uridine Homo sapiens ADP + 3'-C-ethynyluridine 5'-phosphate
-
 ?
ATP + 3'-C-ethynyluridine 5'-diphosphate
-
 Homo sapiens ADP + 3'-C-ethynyluridine 5'-triphosphate
-
 ?
ATP + 3'-C-ethynyluridine 5'-phosphate
-
 Homo sapiens ADP + 3'-C-ethynyluridine 5'-diphosphate
-
 ?
ATP + cytidine
-
 Homo sapiens ADP + CMP
-
 ?
ATP + uridine
-
 Homo sapiens ADP + UMP
-
 ?

Subunits

Subunits Comment Organism
tetramer 4 * 29000, UCK2 forms a tetramer in its active state Homo sapiens

Synonyms

Synonyms Comment Organism
UCK2
-
 Homo sapiens
uridine-cytidine kinase 2
-
 Homo sapiens
uridine/cytidine kinase
-
 Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.5
-
 assay at Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0038
-
 4-(2-[[9-methyl-2-(4-methylphenyl)-5H-[1]benzopyrano[2,3-d]pyrimidin-4-yl]sulfanyl]acetamido)benzoic acid pH 8.5, temperature not specified in the publication Homo sapiens
0.012 0.031 ATP dependent on the assay method, pH 8.5, temperature not specified in the publication Homo sapiens
0.013 0.05 uridine dependent on the assay method, pH 8.5, temperature not specified in the publication Homo sapiens
0.1372
-
 (1Z)-[([5-[(4-fluorophenyl)methyl]-7-oxo-6,7-dihydro-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]methyl)sulfanyl]-N-(2-methylphenyl)ethanimidic acid pH 8.5, temperature not specified in the publication Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0092 0.0166 22°C, 20 mM HEPES (pH 7.2), 100 mM KCl, 2 mM MgCl2, 6-300 microM ATP, 6-300 microM uridine, 1-10 nanoM enzyme UCK2 Homo sapiens N-(4-bromophenyl)-2-[[1-(4-fluorophenyl)-4-hydroxy-1H-pyrazolo[3,4-d]pyrimidin-6-yl]sulfanyl]acetamide
0.0164
-
 pH 8.5, temperature not specified in the publication Homo sapiens N-(4-bromophenyl)-2-[[1-(4-fluorophenyl)-4-hydroxy-1H-pyrazolo[3,4-d]pyrimidin-6-yl]sulfanyl]acetamide
0.0189 0.048 22°C, 20 mM HEPES (pH 7.2), 100 mM KCl, 2 mM MgCl2, 6-300 microM ATP, 6-300 microM uridine, 1-10 nanoM enzyme UCK2 Homo sapiens N-(3,5-dimethylphenyl)-2-[([5-[(4-fluorophenyl)methyl]-7-oxo-2,5,6,7-tetrahydro-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]methyl)sulfanyl]acetamide
0.031
-
 pH 8.5, temperature not specified in the publication Homo sapiens ATP
0.048
-
 pH 8.5, temperature not specified in the publication Homo sapiens N-(3,5-dimethylphenyl)-2-[([5-[(4-fluorophenyl)methyl]-7-oxo-2,5,6,7-tetrahydro-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]methyl)sulfanyl]acetamide
0.05
-
 pH 8.5, temperature not specified in the publication Homo sapiens uridine

General Information

General Information Comment Organism
physiological function the pyrimidine salvage enzyme uridine-cytidine kinase 2 (UCK2) is necessary for uridine salvage. Biological significance of UCK2 in the uridine salvage is measured by incorporating exogenous 5-ethynyl-uridine (5-EU) specifically into cellular RNA Homo sapiens