| Autor: |
Gallego, Rebecca A., Scales, Stephanie, Toledo, Chad, Auth, Marin, Bernier, Louise, Berry, Madeline, Brun, Sonja, Chung, Loanne, Davis, Carl, Diehl, Wade, Dress, Klaus, Eisele, Koleen, Elleraas, Jeff, Ewanicki, Jason, Fobian, Yvette, Greasley, Samantha, Greenwald, Eric C., Johnson, Ted W., Khamphavong, Penney, Lafontaine, Jennifer, Li, Jian, Linton, Angelica, Maestre, Michael, Miller, Nichol, Murtaza, Anwar, Patman, Ryan L., Quinlan, Casey L., Ramms, Dana J., Richardson, Paul, Sach, Neal, Salomon-Ferrer, Romelia, Silva, Francisco, Timofeevski, Sergei, Tran, Phuong, Tran-Dubé, Michelle, Wang, Fen, Wang, Wei, Wythes, Martin, Yang, Shouliang, Zou, Aihua, VanArsdale, Todd, McAlpine, Indrawan |
| Zdroj: |
Journal of Medicinal Chemistry; November 2024, Vol. 67 Issue: 21 p19234-19246, 13p |
| Abstrakt: |
By virtue of its role in cellular proliferation, microtubule-associated serine/threonine kinase-like (MASTL) represents a novel target and a first-in-class (FIC) opportunity to provide a new impactful therapeutic agent to oncology patients. Herein, we describe a hit-to-lead optimization effort that resulted in the delivery of two highly selective MASTL inhibitors. Key strategies leveraged to enable this work included structure-based drug design (SBDD), analysis of lipophilic efficiency (LipE) and novel synthesis. The resulting advanced lead compounds enabled a tumor growth inhibition study which was pivotal in assessing the potential value of MASTL as an oncology therapeutic target. |
| Databáze: |
Supplemental Index |
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