| Hazard Information | Back Directory | [Description]
WM-382 is a PMX inhibitor with antimalarial activity. Oral administration of WM382 cured mice of P. berghei and prevented blood infection from the liver. In addition, WM382 was efficacious against P. falciparum asexual infection in humanized mice and prevented transmission to mosquitoes | [Uses]
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]. | [in vivo]
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. |
| [IC 50]
Plasmodium | [References]
[1] Manuel de LR, et al. The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor toward the Treatment of Malaria. ACS Med Chem Lett. 2022 Oct 12.
[2] Hodder AN, et al. Basis for drug selectivity of plasmepsin IX and X inhibition in Plasmodium falciparum and vivax. Structure. 2022 Jul 7;30(7):947-961.e6. DOI:10.1016/j.str.2022.03.018
[3] Favuzza P, et al. Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of the Malaria Parasite Life Cycle. Cell Host Microbe. 2020 Apr 8;27(4):642-658.e12. DOI:10.1016/j.chom.2020.02.005 |
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