Thymidylate Synthetase

Thymidylate Synthase (TS) EC 2.1.1.45 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.

Products
Background
Literature
Pathways

Inhibitors

Cat No Product Name / Activity
4659 Floxuridine
Thymidylate synthetase inhibitor
3257 5-Fluorouracil
Thymidylate synthetase inhibitor
6185 Pemetrexed
Thymidylate synthetase inhibitor, also inhibits dihydrofolate reductase, GARFT and AICART
4460 Trifluorothymidine
Thymidylate synthetase inhibitor

Thymidylate Synthase (TS) EC 2.1.1.45 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.

Literature for Thymidylate Synthetase

Tocris offers the following scientific literature for Thymidylate Synthetase to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


Cancer Metabolism

Cancer Metabolism Poster

Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the main targets for cancer metabolism researchers. Genetic changes and epigenetic modifications in cancer cells alter the regulation of cellular metabolic pathways. These distinct metabolic circuits could provide viable cancer therapeutic targets.

Cell Cycle & DNA Damage Repair

Cell Cycle & DNA Damage Repair Poster

In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.

Pathways for Thymidylate Synthetase

Apoptosis

Apoptosis Signaling Pathway

Apoptosis is a physiological process for cell death that is critical during aging and development. It may also be referred to as cell 'suicide'. Apoptosis can be triggered by events both inside and outside of the cell.
p53

p53 Signaling Pathway

p53 signaling plays an important role in the co-ordination of the cellular response different types of stress such as DNA damage and hypoxia. The downstream signals lead to apoptosis, senescence and cell cycle arrest.