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- GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH).
GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH).
Citation | “Gs-0976 (Firsocostat): An Investigational Liver-Directed Acetyl-Coa Carboxylase (Acc) Inhibitor For The Treatment Of Non-Alcoholic Steatohepatitis (Nash).”. Expert Opinion On Investigational Drugs, pp. 135-141. . |
Center | Yale University |
Author | Naim Alkhouri, Eric Lawitz, Mazen Noureddin, Ralph DeFronzo, Gerald I Shulman |
Keywords | Acetyl-CoA carboxylase, De Novo Lipogenesis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis |
Abstract |
: lipogenesis (DNL) plays a major role in fatty acid metabolism and contributes significantly to triglyceride accumulation within the hepatocytes in patients with nonalcoholic steatohepatitis (NASH). Acetyl-CoA carboxylase (ACC) converts acetyl-CoA to malonyl CoA and is a rate-controlling step in DNL. Furthermore, malonyl-CoA is an important regulator of hepatic mitochondrial fat oxidation through its ability to inhibit carnitine palmitoyltransferase I. Therefore, inhibiting ACC pharmacologically represents an attractive approach to treating NASH.: This article summarizes preclinical and clinical data on the efficacy and safety of the liver-targeted ACC inhibitor GS-0976 (Firsocostat) for the treatment of NASH. In a phase 2 trial that included 126 patients with NASH and fibrosis, GS-0976 20 mg daily for 12 weeks showed significant relative reduction in liver fat by 29%; however, treatment was associated with an increase in plasma triglycerides with 16 patients having levels >500 mg/dL.: Preclinical and preliminary clinical data support the development of GS-0976 as treatment for NASH. ACC-induced hypertriglyceridemia can be mitigated by fish oil or fibrates, but the long-term cardiovascular effects require further investigations. |
Year of Publication |
2020
|
Journal |
Expert opinion on investigational drugs
|
Volume |
29
|
Issue |
2
|
Number of Pages |
135-141
|
Date Published |
02/2020
|
ISSN Number |
1744-7658
|
DOI |
10.1080/13543784.2020.1668374
|
Alternate Journal |
Expert Opin Investig Drugs
|
PMID |
31519114
|
PMCID |
PMC7063378
|
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