Dihydrofolate reductase inhibitors

Dihydrofolate reductase (DHFR) inhibitors reduce the production of folate (folic acid) required by rapidly dividing cells to make thymine for DNA synthesis.

This antifolate activity is used as cancer chemotherapy because it reduces neoplastic cell proliferation. Methotrexate, pemetrexed and pralatrexate are antifolate drugs used in chemotherapy.

Inhibitors selective for bacterial/microbial DHFR compared to host DHFR are used as as antimicrobial agents. Examples are the antimalarial drugs pyrimethamine and proguanil, and the antibiotic trimethoprim which is used in the treatment of urinary tract infections (UTIs), acute otitis media (AOM) caused by Streptococcus pneumoniae and Haemophilus influenzae and Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP).