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The development process for discovery and clinical advancement of modern antimalarials

Version 2 2024-06-13, 13:19
Version 1 2019-10-03, 08:56
journal contribution
posted on 2024-06-13, 13:19 authored by TD Ashton, SM Devine, JJ Möhrle, B Laleu, JN Burrows, SA Charman, DJ Creek, BE Sleebs
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.

History

Journal

Journal of medicinal chemistry

Volume

62

Pagination

10526-10562

Location

Washington, D.C.

ISSN

0022-2623

eISSN

1520-4804

Language

eng

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Issue

23

Publisher

ACS Publications