# Repositioning a Human Kinase Platelet-Derived Growth Factor Receptor Alpha Type II Inhibitor for Malaria and Inhibition of Hemozoin Formation

## TL;DR

A drug originally designed to inhibit a human kinase was found to also fight malaria by blocking hemozoin formation in parasites.

## Contribution

The paper introduces a new application of a human kinase inhibitor for malaria treatment by targeting hemozoin formation.

## Key findings

- Compound GSK190937 showed strong antiplasmodium activity with an IC50 of 0.22 μM.
- Compounds 20, 23, and 29 improved metabolic stability and antiplasmodium activity.
- The drug series inhibits hemozoin formation, killing late-stage malaria parasites.

## Abstract

A type II Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) human kinase inhibitor GSK190937, with
antiplasmodium
activity against asexual blood stage parasites (PfNF54 IC50 = 0.22 μM) was identified from the Kinase
Chemogenomics Set, a collection of narrow-spectrum human kinase inhibitors.
Medicinal chemistry progression of the hit focused on improving potency,
selectivity, and ADME properties, leading to compounds 20, 23, and 29 with improved microsomal metabolic
stability and asexual blood stage antiplasmodium activity. Mechanism
of action studies showed that this series inhibits hemozoin formation,
killing late-stage trophozoites.