United States-based Gilead Sciences has revealed results from a Phase two, randomised, placebo-controlled trial assessing two doses of GS-0976, an oral, investigational inhibitor of Acetyl-CoA carboxylase
intended for patients with non-alcoholic steatohepatitis (NASH), it was reported yesterday.
today announced results from a Phase 2, randomized, placebo-controlled trial evaluating two doses of GS-0976, an oral, investigational inhibitor of Acetyl-CoA carboxylase
(ACC), in patients with nonalcoholic steatohepatitis (NASH).
Lawitz, MD, reported the promising results of a "proof of concept" open-label study in which the safety and efficacy of 12 weeks' treatment with the oral acetyl-CoA carboxylase
(ACC) inhibitor, GS-0976, was examined in 10 patients with a clinical diagnosis of nonalcoholic fatty liver disease (NAFLD).
The genes encoding levels of Acetyl-CoA carboxylase
(ACC), fatty acid synthase (FAS) and carnitine palmitoyltransferase (CPT) 1 were respectively involved in the regulation of FAS and oxidation.
At the same time, carnitine palmitoyltransferase-I, carnitine palmitoyltransferase-II, acetyl-coa carboxylase
, lipase activity, and lipoprotein lipase in fish tissues were monitored.
subsidiary and its Acetyl-CoA Carboxylase
inhibitor programme, the company said.
The TaqMan primer/probe sets for FASN (Hs01005622_ml), acetyl-CoA carboxylase
[alpha] (ACACA, Hs01046047_ml), sterol regulatory element binding transcription factor 1 (SREBF1, Hs01088691_ml), stearoyl-CoA desaturase (SCD, Hs01682761_ml), nuclear receptor subfamily 1, group H, member (NR1H) 3 (LXR-[alpha], Hs00172885_ml), NR1H2 (LXR-[beta], Hs01027215_gl), RXR-[alpha] (Hs01067640_ml), and actin, beta (ACTS, Hs01060665_gl) were purchased from Applied Biosystems (CA, USA).
2 The examined genes are acetyl-CoA carboxylase
1 (Acaca), apolipoprotein B-100 (Apob), platelet glycoprotein 4 (Cd36), carnitine O-palmitoyltransferase 1, liver isoform (CptIA), diacylglycerol O-acyltransferase 1 (Dgatl), interleukin-6 (Il6), microsomal triglyceride transfer protein large subunit (Mttp), peroxisome proliferator-activated receptor gamma (Pparg), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargcla), 40S ribosomal protein S7 (Rps7), very long-chain acyl-CoA synthetase (Slc27a2), sterol regulatory element-binding protein 1 (Srebfl), transforming growth factor beta-1 (Tgfbl), and tumor necrosis factor (Tnf).
Alterations in malonyl-CoA synthesis by acetyl-CoA carboxylase
and its degradation by malonyl-CoA decarboxylase are important contributors to the high cardiac fatty acid oxidation rates seen in ischemic heart disease and heart failure in obesity and diabetes .
Comment: Biotin is a cofactor for acetyl-CoA carboxylase
, a potentially rate-limiting enzyme in myelin synthesis.
Structure and regulation of acetyl-CoA carboxylase
genes of metazoa.
Insulin inducible enzymes of the path way, namely, acetyl-coA carboxylase
, fatty acid synthase.