Trimetrexate

Trimetrexate (CI-898) is an antibiotic, also a potent and orally active dihydrofolate reductase (DHFR) inhibitor, reducing the production of DNA and RNA precursors and leading to cell death, with IC50 values of 4.74 nM and 1.35 nM for human DHFR and Toxoplasma gondii DHFR. Trimetrexate can also inhibit the growth of various cancer cells. Trimetrexate can be used for researching Pneumocystis carinii pneumonia (PCP) and cancer[1][2][3][4][5].

[1]Fulton, B., et al. Trimetrexate. Drugs 49, 563–576 (1995).|[2]Hopper AT, et al. Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis. J Med Chem. 2019 Feb 14;62(3):1562-1576.|[3]Allegra CJ, et al. Potent in vitro and in vivo antitoxoplasma activity of the lipid-soluble antifolate trimetrexate. J Clin Invest. 1987 Feb;79(2):478-82.|[4]Dethloff LA, et al. Chronic toxicity of the anticancer agent trimetrexate in rats. Fundam Appl Toxicol. 1992 Jul;19(1):6-14.|[5]Grem JL, Voeller DM, Geoffroy F, Horak E, Johnston PG, Allegra CJ. Determinants of trimetrexate lethality in human colon cancer cells. Br J Cancer. 1994 Dec;70(6):1075-84.