# Dihydrofolate reductase (DHFR)

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

## TL;DR

The enzyme that recycles folate so cells can build DNA. Methotrexate blocks it, which is why folinic acid rescue after high-dose methotrexate matters.

## Summary

Dihydrofolate reductase regenerates tetrahydrofolate, the carrier of one-carbon units needed for thymidylate and purine synthesis. Methotrexate is a tight-binding folate analogue that shuts the enzyme down and, as polyglutamates, also inhibits thymidylate synthase; leucovorin bypasses the block in normal tissues, allowing high-dose regimens in acute lymphoblastic leukaemia, osteosarcoma and primary CNS lymphoma. DHFR gene amplification is a classic mechanism of acquired methotrexate resistance, and pemetrexed inhibits DHFR among its folate targets.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Symbol: DHFR
- Class: enzyme
- Biology: NADPH-dependent reductase maintaining the tetrahydrofolate pool; amplified in methotrexate-resistant cells.
- Where found: Acute lymphoblastic leukaemia; Osteosarcoma; Primary CNS lymphoma

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Dihydrofolate_reductase
- UniProt P00374: DHFR: https://www.uniprot.org/uniprotkb/P00374/entry

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Osteosarcoma](https://onco.cc/cancers/osteosarcoma/), [Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/)
- drugs: [Aminopterin](https://onco.cc/drugs/aminopterin/), [Leucovorin (folinic acid)](https://onco.cc/drugs/leucovorin/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/)
- targets: [GART (trifunctional purine synthesis enzyme)](https://onco.cc/targets/gart/), [IMP dehydrogenase (IMPDH2)](https://onco.cc/targets/impdh2/)

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JSON: https://onco.cc/api/v1/entities/dhfr.json