Target Information

Target General Infomation
Target ID
T70101
Former ID
TTDR00956
Target Name
CTP synthase
Gene Name
CTPS1
Synonyms
CTP synthetase; Cytidine 5'-triphosphate synthetase; Cytidine triphosphate synthetase; UTP--ammonia ligase; UTP:ammonia ligase (ADP-forming); Uridine triphosphate aminase; CTPS1
Target Type
Clinical Trial
Disease Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP- dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity.
BioChemical Class
Carbon-nitrogen ligase
UniProt ID
P17812
EC Number
EC 6.3.4.2
Sequence
MKYILVTGGVISGIGKGIIASSVGTILKSCGLHVTSIKIDPYINIDAGTFSPYEHGEVFV
LDDGGEVDLDLGNYERFLDIRLTKDNNLTTGKIYQYVINKERKGDYLGKTVQVVPHITDA
IQEWVMRQALIPVDEDGLEPQVCVIELGGTVGDIESMPFIEAFRQFQFKVKRENFCNIHV
SLVPQPSSTGEQKTKPTQNSVRELRGLGLSPDLVVCRCSNPLDTSVKEKISMFCHVEPEQ
VICVHDVSSIYRVPLLLEEQGVVDYFLRRLDLPIERQPRKMLMKWKEMADRYDRLLETCS
IALVGKYTKFSDSYASVIKALEHSALAINHKLEIKYIDSADLEPITSQEEPVRYHEAWQK
LCSAHGVLVPGGFGVRGTEGKIQAIAWARNQKKPFLGVCLGMQLAVVEFSRNVLGWQDAN
STEFDPTTSHPVVVDMPEHNPGQMGGTMRLGKRRTLFQTKNSVMRKLYGDADYLEERHRH
RFEVNPVWKKCLEEQGLKFVGQDVEGERMEIVELEDHPFFVGVQYHPEFLSRPIKPSPPY
FGLLLASVGRLSHYLQKGCRLSPRDTYSDRSGSSSPDSEITELKFPSINHD
Drugs and Mode of Action
Drug(s) Cyclopentenylcytosine Drug Info Phase 1 Solid tumours [533634]
Acivicin Drug Info Discontinued in Phase 3 Discovery agent [544734]
Inhibitor 2-Methyl-2,4-Pentanediol Drug Info [551393]
Acivicin Drug Info [535177], [537820]
Carbodine Drug Info [537726]
Cyclopentenylcytosine Drug Info [537918]
Cyclopentylcytosine Drug Info [537918]
Cylopentenyl cytosine Drug Info [535125]
Pathways
KEGG Pathway Pyrimidine metabolism
Metabolic pathways
PANTHER Pathway De novo pyrimidine ribonucleotides biosythesis
PathWhiz Pathway Pyrimidine Metabolism
WikiPathways Metabolism of nucleotides
References
Ref 533634Phase I clinical trial of continuous infusion cyclopentenyl cytosine. Cancer Chemother Pharmacol. 1995;36(6):513-23.
Ref 544734Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000775)
Ref 535125Comments on: cylopentenyl cytosine inhibits cytidine triphosphate synthetase in paediatric acute non-lymphocytic leukaemia: a promising target for chemotherapy. A.C. Verschuur et al. Eur J Cancer 2000, 36, 627-635. Eur J Cancer. 2001 Jan;37(2):290.
Ref 535177Trypanosoma brucei CTP synthetase: a target for the treatment of African sleeping sickness. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6412-6. Epub 2001 May 15.
Ref 537726Potent activity of 5-fluoro-2'-deoxyuridine and related compounds against thymidine kinase-deficient (TK-) herpes simplex virus: targeted at thymidylate synthase. Mol Pharmacol. 1987 Aug;32(1):286-92.
Ref 537820Synergistic effects with inhibitors of de novo pyrimidine synthesis, acivicin, and N-(phosphonacetyl)-L-aspartic acid. Cancer Res. 1981 Sep;41(9 Pt 1):3419-23.
Ref 537918Molecular approaches for the treatment of hemorrhagic fever virus infections. Antiviral Res. 1993 Sep;22(1):45-75.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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