Dihydrofolate reductase inhibitor

Dihydrofolate reductase inhibitor

A dihydrofolate reductase inhibitor is a molecule that inhibits the function of dihydrofolate reductase, and is a type of antifolate.

Since folate is needed by rapidly dividing cells to make thymine, this effect may be used to therapeutic advantage. For example, methotrexate is used as cancer chemotherapy because it can prevent neoplastic cells from dividing.[1][2] Bacteria also need DHFR to grow and multiply and hence inhibitors selective for bacterial vs. host DHFR have found application as antibacterial agents.[3]

Tetrahydrofolate synthesis pathway

A variety of drugs act as inhibitors of dihydrofolate reductase:


  1. ^ Huennekens FM (1994). "The methotrexate story: a paradigm for development of cancer chemotherapeutic agents". Adv. Enzyme Regul. 34: 397–419. doi:10.1016/0065-2571(94)90025-6. PMID 7942284. 
  2. ^ McGuire JJ (2003). "Anticancer antifolates: current status and future directions". Curr. Pharm. Des. 9 (31): 2593–613. doi:10.2174/1381612033453712. PMID 14529544. 
  3. ^ Hawser S, Lociuro S, Islam K (March 2006). "Dihydrofolate reductase inhibitors as antibacterial agents". Biochem. Pharmacol. 71 (7): 941–8. doi:10.1016/j.bcp.2005.10.052. PMID 16359642. 
  4. ^ Mui EJ, Schiehser GA, Milhous WK, et al. (2008). Matlashewski, Greg. ed. "Novel Triazine JPC-2067-B Inhibits Toxoplasma gondii In Vitro and In Vivo". PLoS Negl Trop Dis 2 (3): e190. doi:10.1371/journal.pntd.0000190. PMC 2254147. PMID 18320016. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2254147.