WM382

WM382 is an orally active and potent dual plasmepsin IX/X (PMIX/X) inhibitor with IC50 values of 1.4 nM and 0.03 nM, respectively. WM382 has robust in vivo efficacy at multiple stages of the malaria parasite life cycle and an excellent resistance profile[1][2][3].

Research Areas >> Infection

Signaling Pathways >> Others >> Others

IC50: 1.4 nM (PMIX), 0.03 nM (PMX)[1]; 0.006 nM (rPMX)[3]

WM382 shows moderate cytotoxicity against HepG2 cells (IC50=24.8 μM), and inhibits Plasmodium falciparum and P. vivax with an IC50 value of 0.6 nM (P. falciparum)[2][3]. WM382 selectively binds PMV and PMX with Ki values of 13.4 μM and 0.035 nM, respectively[3]. WM382 (1 nM and 100 nM) reminds the time to patent blood infection following injection of 65 h in P. berghei-infected HepG2 in vitro cultures[3].

WM382 (20 mg/kg twice daily or 1-30 mg/kg once daily; p.o.; for 4 d) can clear mouse models of P. berghei and P. falciparum parasites. WM382 is also efficacious against P. falciparum asexual infection in humanized mice and prevents transmission to mosquitoes[3]. Animal Model: Mice infected with P. berghei[3] Dosage: 20 mg/kg Administration: Oral gavage; twice daily for 4 days; monitored for 30 days Result: Cured mice of P. berghei and prevents blood infection from the liver. Animal Model: Humanized nonobese diabetic-severe combined immunodeficiency (NOD-scid) IL2Rgnull mouse model (NSG)[3] Dosage: 1, 3, 10, 30 mg/kg Administration: Oral gavage; once daily for 4 days; monitored for 7 days Result: Cleared of parasitemia by day 6 at 30 mg/kg or day 7 at 3 and 10 ma/kg.