2. Academic Validation
  3. The Development Process for Discovery and Clinical Advancement of Modern Antimalarials

The Development Process for Discovery and Clinical Advancement of Modern Antimalarials

  • J Med Chem. 2019 Dec 12;62(23):10526-10562. doi: 10.1021/acs.jmedchem.9b00761.
Trent D Ashton 1 2,  Shane M Devine 3,  Jörg J Möhrle 4,  Benoît Laleu 4,  Jeremy N Burrows 4,  Susan A Charman 3,  Darren J Creek 3,  Brad E Sleebs 1 2
Affiliations

Affiliations

  • 1 The Walter and Eliza Hall Institute of Medical Research , Parkville , Victoria 3052 , Australia.
  • 2 Department of Medical Biology , The University of Melbourne , Parkville , Victoria 3052 , Australia.
  • 3 Monash Institute of Pharmaceutical Sciences , Monash University , 381 Royal Parade , Parkville , Victoria 3052 , Australia.
  • 4 Medicines for Malaria Venture, ICC , Route de Pré-Bois 20 , 1215 Geneva , Switzerland.
PMID: 31385706 DOI: 10.1021/acs.jmedchem.9b00761
Abstract

Malaria is a devastating disease caused by Plasmodium parasites, resulting in approximately 435000 deaths in 2018. The impact of malaria is compounded by the emergence of widespread resistance to current antimalarial therapies. Recently, a new strategy was initiated to screen small molecule collections against the Plasmodium Parasite enabling the identification of new antimalarial chemotypes with novel modes of action. This initiative ushered in the modern era of antimalarial drug development, and as a result, numerous lead candidates are advancing toward or are currently in human clinical trials. In this Perspective, we describe the development pathway of four of the most clinically advanced modern antimalarials, KAE609, KAF156, DSM265, and MMV048. Additionally, the mechanism of action and life-cycle stage specificity of the four antimalarials is discussed in relation to aligning with global strategies to treat and eliminate malaria. This perspective serves as a guide to the expectations of modern antimalarial drug development.

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