Thymidylate Synthetase (TS) EC 22.214.171.124 is a highly conserved bifunctional enzyme responsible for the reductive methylation of dUMP to dTMP, required for DNA synthesis. TS also functions as a RNA binding protein and its protein levels are linked to chemoresistance in cancer.
|Product Name / Activity
|Thymidylate synthetase inhibitor
|Thymidylate synthetase inhibitor, also inhibits dihydrofolate reductase, GARFT and AICART
Thymidylate Synthetase (TS) EC 126.96.36.199 is a highly conserved bifunctional enzyme, that catalyzes the conversion of deoxyuridine monophosphate (dUMP) and 5,10-methylenetetrahydrofolate to deoxythymidine monophosphate (dTMP) and dihydrofolate. This is an essential metabolic reaction, producing dTMP required for DNA synthesis and dihydrofolate, required for production of purines and pyrimidines and therefore DNA and RNA.
TS also functions as a RNA binding protein, able to regulate its own protein levels through translational autoregulatory feedback mechanisms. It also binds to other RNAs including p35 and myc family transcription factors, leading to a regulatory role in cell cycle and apoptosis.
Inhibition of TS is a mechanism of action of some cytotoxic drugs for cancer treatment including fluoropyrimidines. Inhibition causes an imbalance in deoxynucleotides, leading to increased levels of dUMP causing DNA damage and triggering cell death through p53 and apoptosis. TS activity and/or protein expression correlates with response to fluoropyrimidines: cancer cell lines that express high levels of TS show increased resistance to the cytotoxic and antitumor effects of fluoropyrimidines.
External sources of pharmacological information for Thymidylate Synthetase :
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