Abstract
| Original language | English |
|---|---|
| Journal | Journal of Medicinal Chemistry |
| DOIs | |
| Publication status | Accepted/In press - Aug 2019 |
Cite this
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The Development Process for Discovery and Clinical Advancement of Modern Antimalarials. / Ashton, Trent D.; Devine, Shane; Mohrle, Jorg; Laleu, Benoît; Burrows, Jeremy N.; Charman, Susan; Creek, Darren; Sleebs, Brad E.
In: Journal of Medicinal Chemistry, 08.2019.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - The Development Process for Discovery and Clinical Advancement of Modern Antimalarials
AU - Ashton, Trent D.
AU - Devine, Shane
AU - Mohrle, Jorg
AU - Laleu, Benoît
AU - Burrows, Jeremy N.
AU - Charman, Susan
AU - Creek, Darren
AU - Sleebs, Brad E
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
U2 - 10.1021/acs.jmedchem.9b00761
DO - 10.1021/acs.jmedchem.9b00761
M3 - Article
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
ER -