Date: 2016-04-17
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at The International Liver Congress 2016 in Barcelona, Spain.
Company: Gilead Sciences (USA - CA)
Product: GS-4997
Action mechanism: enzyme inhibitor/kinase inhibitor. GS-4997 is a small-molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1 or mitogen-activated protein kinase kinase kinase 5 (MAP3K5)), which promotes inflammation, apoptosis and fibrosis in settings of increased oxidative stress associated with NASH pathogenesis. Upon oral administration, ASK1 inhibitor GS-4997 binds to the catalytic kinase domain of ASK1, thereby preventing its phosphorylation and activation. This prevents the phosphorylation of downstream kinases, such as c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (p38 MAPK). By preventing the activation of ASK1-dependent signal transduction pathways, GS-4997 prevents the production of inflammatory cytokines, down-regulates the expression of genes involved in fibrosis, suppresses excessive apoptosis and inhibits cellular proliferation.
Disease: NASH (non-alcoholic steatohepatitis)
Therapeutic area: Liver diseases - Hepatic diseases
Country:
Trial details:
Latest news: * On April 16, 2016, Gilead Sciences announced data supporting the development of GS-4997 for the treatment of nonalcoholic steatohepatitis (NASH). The data were presented in oral and poster sessions at The International Liver Congress 2016 in Barcelona, Spain. Results from a Gilead-led preclinical study presented during an oral session (Oral PS-070) demonstrate that GS-444217, a related ASK1 inhibitor, significantly reduced hepatic steatosis, inflammation, fibrosis, serum cholesterol and insulin resistance in mice fed a diet high in fat, cholesterol and sugar. In addition, ASK1 inhibition led to significant changes in plasma metabolites related to bile acid and lipid metabolism.
