Fanotaprim

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Fanotaprim 是一种二氢叶酸还原酶 (DHFR) 抑制剂。 Fanotaprim 抑制刚地弓形虫菌株的生长，TgDHFR IC50 为 1.57 ± 0.11 nM，hDHFR IC50 为 308 ± 71 nM，hDHFR 与 TgDHFR 选择性比为 196。

Fanotaprim is a dihydrofolate reductase (DHFR) inhibitor. Fanotaprim inhibits the growth of T. gondii strains with a TgDHFR IC50 of 1.57 ± 0.11 nM and a hDHFR IC50 of 308?±?71 nM and a hDHFR to TgDHFR selectivity ratio of 196.(In Vitro):Fanotaprim had a parasiticidal EC50 of 13 nM against the type I RH strain of T. gondii. In human MCF-7 cells, Fanotaprim had an EC50 value of 7300 nM. The selectivity of Fanotaprim in the cell-based assays is in line with its DHFR selectivity profiles of 200-fold.(In Vivo):Fanotaprim had moderate mouse liver microsome (MLM) intrinsic clearance (Clint) of 56.3 mL min–1 kg–1, which is 63% of mouse liver blood flow (LBF). Fanotaprim has low to moderate clearance of 10.6 mL min–1 kg–1, a volume of distribution of 1.14 L/kg, and a half-life of 3.9 h after a 1.0 mg/kg, iv dose. Oral bioavailability after a 0.83 mg/kg po dose was 47.3% with a Cmax of 178 ng/mL 30 min after dosing. The unbound fraction (%) in mouse plasma is 8.7 ± 0.2 and in brain homogenate 2.4 ± 0.3, determined using an equilibrium dialysis method. Fanotaprim was freely permeable into the mouse CNS at 0.5 h after a 10 mg/kg oral dose; the concentration in brain was 2560 ± 240 ng/g and in blood 1610 ± 580 ng/mL, giving a brain to blood ratio of 1.7 ± 0.6.

Fanotaprim shows parasiticidal and antiproliferative effects with EC50s 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 EC50s ranging 7.6~ 29.8 nM (GT1, ME49, CTG, RUB and VAND).

Fanotaprim (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 CL, Vd, and t1/2 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, Cmax, Tmax, and AUC0-last of 47.3%, 178 ng/mL, 0.05 hours and 750 ng h/mL, respectively. 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.

——

Cell Cycle/DNA Damage

DHFR

EZH2 Y641N

——

——

2120282-75-7

378.43

C19H22N8O

>98% (HPLC)

In Vitro:?DMSO : 33.33 mg/mL (88.07 mM)

N/A

——

(-20℃)

With Ice Pack

≥ 2 years