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Updated: May 5, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Piperazine oxadiazole inhibitors of acetyl-CoA carboxylase
Matthew P Bourbeau1, Aaron Siegmund, John G Allen
1Therapeutic Discovery, ‡Metabolic Diseases Research, §Pharmacokinetics/Drug Metabolism, and ∥Comparative Biology & Safety Sciences, Amgen Inc. , 1 Amgen Center Dr, Thousand Oaks, California 91320, United States.
Abstract:
Acetyl-CoA carboxylase (ACC) is a target of interest for the treatment of metabolic syndrome. Starting from a biphenyloxadiazole screening hit, a series of piperazine oxadiazole ACC inhibitors was developed. Initial pharmacokinetic liabilities of the piperazine oxadiazoles were overcome by blocking predicted sites of metabolism, resulting in compounds with suitable properties for further in vivo studies. Compound 26 was shown to inhibit malonyl-CoA production in an in vivo pharmacodynamic assay and was advanced to a long-term efficacy study. Prolonged dosing with compound 26 resulted in impaired glucose tolerance in diet-induced obese (DIO) C57BL6 mice, an unexpected finding.
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