| Autor: |
Manuel de Lera Ruiz, Paola Favuzza, Zhuyan Guo, Lianyun Zhao, Bin Hu, Zhiyu Lei, Dongmei Zhan, Nicholas Murgolo, Christopher W. Boyce, Marissa Vavrek, Jennifer Thompson, Anna Ngo, Kate E. Jarman, Johnathan Robbins, Justin Boddey, Brad E. Sleebs, Kym N. Lowes, Alan F. Cowman, David B. Olsen, John A. McCauley |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
ACS Medicinal Chemistry Letters. 13:1745-1754 |
| ISSN: |
1948-5875 |
| DOI: |
10.1021/acsmedchemlett.2c00355 |
| Popis: |
Drug resistance to first-line antimalarials-including artemisinin-is increasing, resulting in a critical need for the discovery of new agents with novel mechanisms of action. In collaboration with the Walter and Eliza Hall Institute and with funding from the Wellcome Trust, a phenotypic screen of Merck's aspartyl protease inhibitor library identified a series of plasmepsin X (PMX) hits that were more potent than chloroquine. Inspired by a PMX homology model, efforts to optimize the potency resulted in the discovery of leads that, in addition to potently inhibiting PMX, also inhibit another essential aspartic protease, plasmepsin IX (PMIX). Further potency and pharmacokinetic profile optimization efforts culminated in the discovery of |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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