| Autor: |
Charu Chaudhry, Ping Zhang, Kyoung S. Kim, William J. Pitts, Cornelius Lyndon A M, Lynn M. Abell, Hart Amy C, Kevin O’Malley, Junqing Guo, Brian Carpenter, Hao Lu, Ramesh Padmanabha, Patrick J. Shaw, Mertzman Michael E, Kevin Kish, Andrew E Douglas, Matthew Pokross, John E. Macor, Deepa Calambur, Carolyn A. Weigelt |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
ACS Med Chem Lett |
| ISSN: |
1948-5875 |
| DOI: |
10.1021/acsmedchemlett.9b00065 |
| Popis: |
[Image: see text] Necroptosis has been implicated in a variety of disease states, and RIPK3 is one of the kinases identified to play a critical role in this signaling pathway. In an effort to identify RIPK3 kinase inhibitors with a novel profile, mechanistic studies were incorporated at the hit triage stage. Utilization of these assays enabled identification of a Type II DFG-out inhibitor for RIPK3, which was confirmed by protein crystallography. Structure-based drug design on the inhibitors targeting this previously unreported conformation enabled an enhancement in selectivity against key off-target kinases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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