Apoptosis signal regulating kinase 1 (ASK1) is a widely expressed redox-sensitive serine threonine kinase that activates inflammatory, fibrotic and apoptotic signaling. Pathological imbalances in cellular redox homeostasis and the resultant activation and dysregulation of downstream ASK1 signaling have been implicated in the pathogenesis of diseases such as diabetic kidney disease (DKD), pulmonary arterial hypertension (PAH), and nonalcoholic steatohepatitis (NASH). This presentation describes the research effort leading to the identification of Selonsertib, a first-in-class, potent, and highly selective inhibitor of ASK1. In murine models of NASH and liver fibrosis, ASK1 inhibition reduced the amount of steatosis and fibrosis and decreased the circulating levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as compared to normal controls. In a Phase 1 trial, Selonsertib demonstrated an excellent safety profile and a t<sub>1/2</sub> amenable to QD dosing.

Discovery of selonsertib (GS-4997): A first in class, selective inhibitor of apoptosis signal-regulating kinase 1

253rd National Meeting (2017)

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