Developing kinase inhibitors for malaria: an opportunity or liability?

Highly druggable and essential to almost all aspects of cellular life, the protein and phosphoinositide kinase gene families offer a wealth of potential targets for pharmacological modulation for both noncommunicable and infectious diseases. Despite the success of kinase inhibitors in oncology and other disease indications, targeting kinases comes with significant challenges. Key hurdles for kinase drug discovery include selectivity and acquired resistance. The phosphatidylinositol 4-kinase beta inhibitor MMV390048 showed good efficacy in Phase 2a clinical trials, demonstrating the potential of kinase inhibitors for malaria treatment. Here we argue that the potential benefits of Plasmodium kinase inhibitors outweigh the risks, and we highlight the opportunity for designed polypharmacology to reduce the risk of resistance.

Automated summary

The protein and phosphoinositide kinase gene families are highly druggable and essential in cellular life, providing potential targets for pharmacological modulation in various diseases. However, targeting kinases comes with challenges of selectivity and acquired resistance. The success of a kinase inhibitor in malaria treatment shows the potential benefits of Plasmodium kinase inhibitors and the opportunity for reducing resistance through designed polypharmacology.