Bempedoic acid
ATP citrate lyase inhibitor / Inhibitor of ATP citrate lyase (ACL) and activator of AMPK used in the treatment of hypercholesterolemia.1,2 In vivo, the active molecule is the CoA ester.2 Bempedoic acid requires activation by very long-chain acyl-CoA-synthetase (ACSVL1) – the absence of ACSVL1 in skeletal muscle provides a mechanistic basis for its use in statin-intolerant patients.3 LDL receptor upregulation, decreased LDL-C, and attenuation of atherosclerosis activities are independent of AMPK activation. It significantly cuts the risk of major cardiovascular events.4 Combination treatment of breast and pancreatic cancer cell lines with bempedoic acid and CDK4/6 inhibitors reduced cell growth and invasion.5 It displays anti-inflammatory activity possibly through both ACL inhibition6,7 and AMPK activation8.
Biochemicals & reagents
738606-46-7
ESP 55016; ETC-1002
1) Cramer et al. (2004), Effects of a novel dual lipid synthesis inhibitor and its potential utility in treating dyslipidemia and metabolic syndrome; J. Lipid Res., 45 P1289 2) Pinkosky et al. (2013), AMP-activated protein kinase and ATP-citrate lyase are two distinct molecules targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism; J. Lipid Res., 54 134 3) Pinkosky et al. (2016), Liver-specific ATP-citrate lyase inhibition by bempedoic aicd decreases LDL-C and attenuates atheroscleosis; Nat. Commun., 7 13457 4) Nissen et al. (2023), Bempedoic acid and cardiovascular outcomes in statin-intolerant patients; N. Engl. J. Med., online March 4, 2023 5) Velez et al. (2023), Combined inhibition of ACLY and CDK4/6 reduces cancer cell growth and invasion; Oncol. Rep., 49 32 6) Samsoonday et al. (2017), Prevention of Diet-Induced metabolic dysregulation, inflammation, and atherosclerosis in ldlr-/- mice by treatment with the ATP-Citrate lyase inhibitor bempedoic acid; Arterioscler. Thromb. Avsc. Biol., 37 647 7) Verberk et al. (2021), The multifaceted therapeutic value of targeting ATP-citrate lyase in atheroscleosis; Trends Mol. Med., 27 1095 8) Filippov et al. (2013), ETC-1002 regulates immune response, leukocyte homing, and adipose tissue inflammation via LKB1-dependent activation of macrophage AMPK; J. Lipid Res., 54 2095
-20°C
PATHWAY: Fatty acid metabolism; Cholesterol metabolism; AMPK pathway -- DISEASE AREA: Atherosclerosis; Heart diseaseCancer; Inflammation