Thymidylate synthase (TYMS)
The enzyme that makes the thymine building block of DNA. Fluorouracil, capecitabine and pemetrexed jam it, starving dividing cells of thymidine.
Overview
Thymidylate synthase methylates dUMP to dTMP, the only de novo source of thymidine for DNA synthesis. Fluorouracil, given directly or as the oral prodrug capecitabine, is converted to FdUMP, which forms a stable ternary complex with the enzyme and its folate cofactor; leucovorin (folinic acid) is added to stabilise that complex, which is why FOLFOX and FOLFIRI include it. Pemetrexed inhibits thymidylate synthase alongside other folate enzymes. High tumour TYMS expression is associated with fluoropyrimidine resistance, and DPD deficiency causes severe fluoropyrimidine toxicity.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · The enzyme that makes the thymine building block of DNA. Fluorouracil, capecitabine and pemetrexed jam it, starving dividing cells of thymidine.
- 1 · What it is
The enzyme that makes the thymine building block of DNA. Fluorouracil, capecitabine and pemetrexed jam it, starving dividing cells of thymidine.
- 2 · What goes wrong in cancer
Folate-dependent enzyme converting dUMP to dTMP; inhibited by FdUMP in a ternary complex with 5,10-methylenetetrahydrofolate.
- 3 · How drugs use it
No product in this corpus aims at Thymidylate synthase (TYMS) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Biology
Folate-dependent enzyme converting dUMP to dTMP; inhibited by FdUMP in a ternary complex with 5,10-methylenetetrahydrofolate.
- Gastrointestinal cancers treated with fluoropyrimidines
- Non-squamous lung cancer and mesothelioma treated with pemetrexed
Latest papers
topQuery for this target: (TITLE:"Thymidylate synthase" OR ABSTRACT:"Thymidylate synthase" OR TITLE:"TYMS" OR ABSTRACT:"TYMS") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Thymidylate synthase (TYMS), not a curated reading list.
Similar pages
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