DSM502

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

DSM502 是一种基于吡咯的二氢乳清酸脱氢酶 (DHODH) 抑制剂。DSM502 对 Plasmodium DHODH 和 Plasmodium 寄生虫表现出纳摩尔级效力，对哺乳动物 DHODH 没有抑制作用。

DSM502 is a pyrrole-based Dihydroorotate Dehydrogenase (DHODH) inhibitor. DSM502 exhibits nanomolar potency againsts Plasmodium DHODH and Plasmodium parasites, with no inhibition of mammalian DHODHs.

DSM502 shows inhibitory activity against P. falciparum DHODH (PfDHODH, IC50=20 nM), P. vivax DHODH (PvDHODH, IC50=14 nM) and Pf3D7 cells (EC50=14 nM), with no inhibition of the human enzyme.

DSM502 (10 and 50 mg/kg; p.o. once daily for 4 days) results in 97% parasite clearance in confirmatory SCID study compared to 85% clearance in the GSK study.DSM502 (18.3 and 50 mg/kg; a single p.o.) exhibits high oral bioavailability (>100%, >100%), apparent t1/2 (2.6, 3.6 h) and Cmax (8.4, 42.3 μM) in mice.DSM502 (2.8 mg/kg; a single i.v.) exhibits apparent t1/2 (2.8 h), plasma clearance (26.1 mL/min/kg), and Vss (1.2 L/kg) in mice.Animal Model:SCID mice (23-36 g) were inoculated with parasites Dosage:10 and 50 mg/kg Administration:P.o. once daily for 4 days starting on day 3 after mice had been inoculated with parasites Result:Resulted in 97% parasite clearance compared to 85% clearance in the GSK study.The 10 mg/kg mouse died on day 5.

——

Metabolic Enzyme/Protease

Dehydrogenase

Dehydrogenase | Parasite

——

——

2426616-55-7

323.31

C16H16F3N3O

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 250 mg/mL (773.25 mM; 超声助溶 )

Cc1c(Cc2ccc(nc2)C(F)(F)F)c[nH]c1C(=O)NC1CC1

——

(-20℃)

With Ice Pack

≥ 2 years