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Request The Product List ofAcetyl-CoA Carboxylase (ACC) Acetyl-CoA Carboxylase (ACC)

Acetyl-CoA carboxylase (ACC) is a biotin carboxylase that catalyzes the ATP-dependent condensation of acetyl-CoA and carbonate to form malonyl-CoA. The malonyl-CoA produced by ACC serves two major physiologic functions. It is an essential and rate-limiting substrate for de novo lipogenesis (DNL), and it acts as an allosteric inhibitor of the enzyme carnitine-palmitoyl transferase I (CPT-1). Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer.

Acetyl-CoA carboxylase (ACC) in mammals is encoded by two related enzymes ACC1 and ACC2, which catalyze the ATP dependent carboxylation of acetyl-CoA to form malonyl-CoA. ACC1 encodes a cytoplasmic isoform that is thought to be the predominant isoform controlling FASyn, whereas ACC2 is tethered to the mitochondrial outer membrane, where localized malonyl-CoA production blocks CPT-1 function to prevent fatty acids from entering the mitochondria to undergo fatty acid oxidation (FAOxn).

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ND-654 (ND654) is a novel potent, liver-specific acetyl-CoA carboxylase (ACC) inhibitor with IC50 of 3/8 nM for human ACC1/ACC2, respectively; inhibits HepG2 cell fatty acid synthesis with an EC50 of 14 nM, and reduces both rat hepatic malonyl-CoA and rat hepatic fatty acid synthesis with ED50 values of 0.34 mg/kg and 0.30 mg/kg at Cmax, respectively; mimics the effects of ACC phosphorylation inhibits hepatic DNL and the development of HCC, selectively targets the liver and inhibits HCC proliferation, improves survival of tumor-bearing rats when used alone and in combination with the multi-kinase inhibitor sorafenib.




TOFA (RMI14514, MDL14514) is an indirect, allosteric inhibitor of Acetyl-CoA carboxylase-α (ACCA) and fatty acid synthesis; converted to TOFyl-CoA, exerts an allosteric inhibition on ACCA; lowers blood lipids and inhibits fatty acid synthesis with minimal effects on liver weight and liver fat content; also induces human cancer cell apoptosis through disturbing their fatty acid synthesis.

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