# Thymidylate synthase (TYMS)

Source: https://onco.cc/targets/tyms/  
OnCo record `tyms` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The enzyme that makes the thymine building block of DNA. Fluorouracil, capecitabine and pemetrexed jam it, starving dividing cells of thymidine.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Symbol: TYMS
- Class: enzyme
- Biology: Folate-dependent enzyme converting dUMP to dTMP; inhibited by FdUMP in a ternary complex with 5,10-methylenetetrahydrofolate.
- Where found: Gastrointestinal cancers treated with fluoropyrimidines; Non-squamous lung cancer and mesothelioma treated with pemetrexed

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Thymidylate_synthase
- UniProt P04818: TYMS: https://www.uniprot.org/uniprotkb/P04818/entry

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Doxifluridine](https://onco.cc/drugs/doxifluridine/), [Floxuridine](https://onco.cc/drugs/floxuridine/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Leucovorin (folinic acid)](https://onco.cc/drugs/leucovorin/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Raltitrexed](https://onco.cc/drugs/raltitrexed/)
- targets: [GART (trifunctional purine synthesis enzyme)](https://onco.cc/targets/gart/)

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