Last Updated: 29/06/2026
Aspartyl protease inhibitors as antimalarials
Objectives
The proposed research aims to increase potency against the parasite whilst maintaining selectivity, progressing to a lead optimisation stage discovery program.
Malaria is one of the world’s most devastating diseases of humans and results in over 450,000 deaths annually. Novel therapies are urgently required to populate the antimalarial clinical portfolio, as the current therapeutics that treat this disease are becoming less effective due to emerging resistance. A collaboration between Dr David Olsen from Merck & Co., Kenilworth, NJ USA (known as MSD outside the US and Canada) and Professor Alan Cowman from the Walter and Eliza Hall Institute (WEHI), has demonstrated that malaria aspartyl protease enzymes are an attractive drug target, as they perform essential functions for survival in blood, sexual and liver stages of the parasite life cycle. Through screening aspartyl protease inhibitor libraries, the collaboration has identified novel drug-/ike hit compounds that are potently active against the malaria parasite.
- Article: Basis for drug selectivity of plasmepsin IX and X inhibition in Plasmodium falciparum and vivax - [Structure, 2022]
- Article: The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor toward the Treatment of Malaria - [ACS Med Chem Lett, 2022]
- Article: Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of the Malaria Parasite Life Cycle - [Cell Host Microbe, 2020]
Jun 2020 — Jul 2020
$136,104
