Fanotaprim (C09-1134-025)

Fanotaprim is a dihydrofolate reductase (DHFR) inhibitor with IC 50 s of 1.57 and 308 nM for tg DHFR ( Toxoplasma gondii DHFR) and hDHFR (human DHFR), respectively. Fanotaprim has the potential for the research of toxoplasmosis.In VitroFanotaprim shows parasiticidal and antiproliferative effects with EC 50 s of 13 and 7300 nM against the type I RH strain of T. gondii and MCF-7 cells, respectively. Fanotaprim shows ability to inhibit the growth of T. gondii strains in vitro with EC 50 s ranging 7.6~ 29.8 nM (GT1, ME49, CTG, RUB and VAND). MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoFanotaprim (1-10 mg/kg; p.o.; daily; beginning on day 1 through day 7) shows highly effective in control of acute infection by highly virulent strains of T. gondii in the murine model . Fanotaprim (1mg/kg; i.v; mouse) shows C L , V d , and t 1/2 values of 10.6 mL/min/kg, 1.14 L/kg, and 3.9 hours, respectively . Fanotaprim (0.83 mg/kg; p.o; mouse) shows F, C max , T max , and AUC 0-last of 47.3%, 178 ng/mL, 0.05 hours and 750 ng h/mL, respectively . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: CD-1female mice (murine model of acute toxoplasmosis) Dosage: 1-10 mg/kg Administration: p.o.; daily; beginning on day 1 through day 7 Result: Mice were monitored for survival for 30 days within termittent IVIS monitoring. At doses of 10 mg/kg Fanotaprim, q.d. or b.i.d. for 7 days, yielded 100% survival for 30 days. Specification: 10mM in DMSO Molecular Formula: C19H22N8O Molecular Weight: 378.43