Methotrexate is an antimetabolite and antifolate drug used in cancer therapy, autoimmune disorders, and ectopic pregnancies. However, its therapeutic efficacy is often limited by its potential to cause severe toxicity. Methotrexate inhibits dihydrofolate reductase (DHFR), an enzyme critical for the synthesis of nucleotides. This leads to a depletion of tetrahydrofolate, impairing DNA synthesis and repair, which can harm rapidly dividing cells, including cancerous and healthy cells, and result in toxicity.
