Lead optimisation of a series of antimalarial plasmepsin IX/X beta-hydroxyethylamine based inhibitors

Malaria is a disease that is transmitted by the bite of the female Anopheles mosquito and is caused by a parasite belonging to Plasmodium genus. One of the challenges in drug treatment of this parasite is its complex life cycle which involves development in the mosquito, and two separate stages of development within the liver and red blood cells of the human host. Finding drug molecules that can target the parasite at all three development stages is the holy grail of antimalarial drug discovery since this will enable an highly effective antimalarial “triple-hit” to be exerted. Recently, two enzymes have been characterised known as Plasmepsins IX and X. These enzymes have been shown to be key to the parasite development in mosquito, blood and liver stages; inhibition of these proteins not only prevents the parasite invading human red blood cells but inhibition of plasmepsin X prevents the parasite from escaping the human red blood cell to continue the infection cycle. Recently, a breakthrough was made that showed a class of drug known as a protease inhibitor can inhibit these enzymes. This class of drug, which are chemically related to the HIV protease inhibitor drugs used for over two decades, have excellent parasite killing activity in test-tube experiments in the laboratory. More recently, one of these prototype drugs was shown to cure mice infected with Plasmodium species demonstrating the potential for development of an oral treatment of malaria infected human patients.

Project details

Drug-based Strategies
Product Development

Feb 2024 — Jan 2026

$1.43M

Italy
Switzerland
United Kingdom