Folate analogues

Folate analogues are a broad class of molecules designed to mimic or antagonize the biological actions of folic acid (vitamin B9), a key cofactor for nucleotide and methionine synthesis. These molecules include several antimetabolite chemotherapy agents (such as methotrexate, pemetrexed, and raltitrexed), as well as supplements and rescue agents like leucovorin. Many antifolates act by competitively inhibiting folate-dependent enzymes such as dihydrofolate reductase or thymidylate synthase, thereby disrupting DNA replication and cellular proliferation. They play an essential role in cancer treatment, immune modulation, and anti-infective therapy. Folate analogues are not a target themselves, but a class of therapeutics and probes that exert their action on key molecular targets involved in folate metabolism, such as the folate receptor, DHFR, and other folate transporters and enzymes.

Other names

folic acid analoguesantifolatesfolate antagonistsfolic acid derivatives

Competitive inhibition of folate-dependent enzymes, including dihydrofolate reductase (DHFR), thymidylate synthase, and others; Disruption of nucleotide synthesis (purines, thymidylate); Rescue or modulation of folate pathways (with reduced or alternative folate forms)