Small molecule
PubChem CID 126941
Methotrexate
Trexall
- Mechanism of action
- Dihydrofolate reductase inhibitor (antimetabolite)
- In plain language
- Blocks an enzyme cancer and inflammatory cells need to copy their DNA, slowing down abnormal cell growth and calming an overactive immune system.
- How it works
- Methotrexate inhibits dihydrofolate reductase, preventing the reduction of dihydrofolate to tetrahydrofolate, a required carrier for one-carbon transfer reactions in purine and thymidylate synthesis. This blocks DNA synthesis, repair, and cellular replication, an effect most pronounced in rapidly proliferating cells such as malignant cells and activated immune cells. In rheumatoid arthritis and psoriasis, the precise mechanism is not fully established, but the drug is believed to exert anti-inflammatory and immunomodulatory effects distinct from its antifolate/antiproliferative action at the low doses used in these conditions. Effects are dose- and schedule-dependent, with high-dose oncology regimens requiring leucovorin rescue to protect normal cells.
- Therapeutic applications
- Indicated as part of combination chemotherapy maintenance regimens for acute lymphoblastic leukemia; for mycosis fungoides and relapsed/refractory non-Hodgkin lymphoma in adults; for rheumatoid arthritis in adults; for polyarticular juvenile idiopathic arthritis in pediatric patients; and for severe, recalcitrant, disabling psoriasis in adults.
- Class
- Small molecule
- Therapeutic area
- Oncology / Rheumatology / Dermatology
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