The Discovery of Bridged Benzoazepine Amides as Selective Allosteric Modulators of RIPK1
Year: 2025
Type: article
Abstract: Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in necroptosis, a form of inflammatory, caspase-independent, programmed cell death. Allosteric inhibitors of RIPK1 have been shown to block necroptotic cell death and thus may offer potential therapeutic opportunities across a range of infectious, autoimmune, and neurodegenerative diseases. We report the structure-informed discovery of a novel series of bridged benzoazepine amides as part of our efforts to develop a CNS-penetrant small-molecule inhibitor of RIPK1 with a low projected oral human dose.
Source: ACS Medicinal Chemistry Letters
Authors: Joanna L. Chen, Joey L. Methot, Matthew J. Mitcheltree, Andrew Musacchio, Emily B. Corcoran, Guo Feng, Alfred Lammens, Klaus Maskos, Rachel L. Palte, Meredith M. Rickard, Karin M. Otte, My S. Mansueto, Sriraman Venkat, Christopher Sondey, Maren Thomsen, Charles A. Lesburg, Xavier Fradera, Matthew J. Fell, Erin F. DiMauro, Phieng Siliphaivanh
Institution: Merck & Co., Inc., Rahway, NJ, USA (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4409430537