HS-1371, a novel kinase inhibitor of RIP3-mediated necroptosis.

ABSTRACT: Necroptosis is a type of programmed cell death that usually occurs under apoptosis-deficient conditions. Receptor-interacting protein kinase-3 (RIP3, or RIPK3) is a central player in necroptosis, and its kinase activity is essential for downstream necroptotic signaling events. Since RIP3 kinase activity has been associated with various diseases, the development of specific RIP3 inhibitors is an attractive strategy for therapeutic application. In this study, we identified a potent RIP3 inhibitor, HS-1371, by the extensive screening of chemical libraries focused on kinases. HS-1371 directly binds to RIP3 in an ATP-competitive and time-independent manner, providing a mechanism of action. Moreover, the compound inhibited TNF-induced necroptosis but did not inhibit TNF-induced apoptosis, indica

SUBMITTER: Park HH 

PROVIDER: S-EPMC6148246 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature