selonsertib

Selonsertib is an investigational small molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1), a serine/threonine kinase that is activated by oxidative stress. Activation of ASK1 leads to the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK), which in turn activate stress response pathways that promote hepatic inflammation, apoptosis, and fibrosis. Developed by Gilead Sciences (originally acquired from Nimbus Therapeutics), selonsertib was primarily evaluated for the treatment of nonalcoholic steatohepatitis (NASH) with advanced fibrosis or cirrhosis. Despite promising Phase 2 results, Phase 3 trials (STELLAR-3 and STELLAR-4) failed to meet their primary endpoints of fibrosis improvement without worsening of NASH. Selonsertib has also been investigated for other conditions involving oxidative stress and fibrotic pathways, including diabetic kidney disease, pulmonary arterial hypertension, and alcoholic hepatitis.

Other names

selonsertib