Receptor-interacting protein kinase 1 (RIP1K), a key component of the cellular necroptosis pathway, has gained recognition as an exciting therapeutic target. Pharmacologic inhibition or genetic modulation of RIP1K has shown promise in models of disease ranging from acute ischemic conditions, chronic inflammation, and neurodegeneration. Accordingly, there has been a surge of interest in developing small molecule inhibitors of RIP1K. We present here a class of RIP1K inhibitors that is distinguished by a lack of a lipophilic aromatic group present in most literature inhibitors that typically occupies a hydrophobic back pocket of the protein active site. Despite not having this ubiquitous feature of many RIP1K inhibitors, we were able to obtain compounds with good potency, selectivity, and pharmacokinetics.<br/>

Potent and selective inhibitors of receptor-interacting protein kinase 1 that lack an aromatic back pocket group

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.