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]}. IC50 & Target:IC₅₀: 4.74 nM (human DHFR), 1.35 nM (Toxoplasma gondii DHFR)^[1] In Vitro: Trimetrexate (0.1 μM, 18 h) completely inhibits proliferation of toxoplasma in murine macrophages^[3].
Trimetrexate (1 μM) can cross the toxoplasma cell membrane and rapidly reaches high intracellular concentrations (108 pmol/10⁷ cells within 10 min) ^[3].
Trimetrexate (0.1 mM; 24 h) inhibits cell growth by 50-60% in SNU-C4 and NCI-H630 cell lines^[5].
Trimetrexate (1 and 10 mM; 24 h) produces lethality and inhibits DHFR in C4 cells^[5]. In Vivo: Trimetrexate (180 mg/kg or 30 mg/kg; p.o. or i.p.; daily) extends the median survival of the toxoplasma infected mice and shows antitoxoplasma activity^[3]. Trimetrexate (0-30 mg/kg; i.v.; once daily for 5days) shows chronic toxicity in rats^[4].