DSM502

Research use only, not for human use.

DSM502 DSM502 is a dihydroorotic acid dehydrogenase (DHODH) inhibitor with antimalarial activity that inhibits Plasmodium DHODH and can be used as a lead for antimalarial compounds.

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.

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Metabolic Enzyme/Protease

Dehydrogenase

Dehydrogenase | Parasite

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2426616-55-7

323.31

C16H16F3N3O

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (773.25 mM; Ultrasonic )

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

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(-20℃)

With Ice Pack

≥ 2 years