Dihydrofolate reductase (DHFR)
The enzyme that recycles folate so cells can build DNA. Methotrexate blocks it, which is why folinic acid rescue after high-dose methotrexate matters.
Overview
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.
- 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 recycles folate so cells can build DNA. Methotrexate blocks it, which is why folinic acid rescue after high-dose methotrexate matters.
- 1 · What it is
The enzyme that recycles folate so cells can build DNA. Methotrexate blocks it, which is why folinic acid rescue after high-dose methotrexate matters.
- 2 · What goes wrong in cancer
NADPH-dependent reductase maintaining the tetrahydrofolate pool; amplified in methotrexate-resistant cells.
- 3 · How drugs use it
No product in this corpus aims at Dihydrofolate reductase (DHFR) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Biology
NADPH-dependent reductase maintaining the tetrahydrofolate pool; amplified in methotrexate-resistant cells.
- Acute lymphoblastic leukaemia
- Osteosarcoma
- Primary CNS lymphoma
Latest papers
topQuery for this target: (TITLE:"Dihydrofolate reductase" OR ABSTRACT:"Dihydrofolate reductase" OR TITLE:"DHFR" OR ABSTRACT:"DHFR") 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 Dihydrofolate reductase (DHFR), not a curated reading list.
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