Plasmepsin V as a malaria drug target
Challenge

To develop new therapies for the treatment of malaria.

How did the facility help?

Approximately half of the world’s population is at risk of contracting malaria each year, with more than 200 million people infected. Malaria kills up to 700,000 people each year, predominantly children under the age of five. The parasite has developed resistance to many current antimalarial drugs rendering them less effective, making the search for new targets that can kill all species of malaria critical.

Plasmepsin V (PMV) is a protein essential for protein export in malaria parasites and inhibition kills parasites at the trophozoite stage. The WEHI Screening Lab is working in collaboration with several Divisions within the Institute as well as with the Pharmaceutical company Merck. We have developed a complex screening cascade to identify small molecule inhibitors of PMV.

In the last reporting period ~1,300 aspartyl protease inhibitors have been screened in the established biochemical assays. We are also currently developing an additional three assays to comprise a selectivity panel against other members of the plasmepsin protein family.

Outcome

A medicinal chemistry program has commenced to improve the potency of the inhibitors identified in the screening campaign. Two publications in top medicinal chemistry journals have been published in the current reporting period.

Background

The WEHI HTCS facility has been in operation since 2003. During this time the focus of the facility has been translational science and its operation has underpinned the WEHI’s participation in a number of successful translational ventures.

High Throughput Chemical Screening

Level 14, 330 Collins St

Melbourne 3000 VIC

Call

T: +61 (07) 3735 4433

©2019 Therapeutic Innovation Australia

Enabled by

NCRIS-PROVIDER-RGB-REV.png