title: ETC-1002: a future option for lipid disorders?
abstract: ETC-1002 is a new investigational low density lipoprotein cholesterol (LDL-C)-lowering agent (Esperion Therapeutics, Inc.). ETC-1002 is a dicarboxylic acid derivative with a novel mechanism of action targeting two hepatic enzymes--adenosine triphosphate-citrate lyase (ACL) and adenosine monophosphate-activated protein kinase (AMPK), inhibiting sterol and fatty acid synthesis and promoting mitochondrial long-chain fatty acid oxidation. This agent is currently in phase II clinical research. Available data report that ETC-1002 significantly decreased LDL-C levels (up to 32%) in both patients with normal and elevated baseline levels of triglycerides. Such beneficial effect is superior to currently approved non-statin lipid lowering agents. The levels of apolipoprotein B (apoB) and non-high density lipoprotein cholesterol (non-HDL-C) were also reduced with beneficial effect on other cardiometabolic factors such as inflammatory markers, blood pressure and body weight. Although, the safety and tolerability of ETC-1002 needs to be confirmed in ongoing and future, larger studies, this agent has, so far, been generally safe and well tolerated. This novel, oral, once-daily, small molecule may lead to effective LDL-C lowering treatment in hypercholesterolaemic subjects who are statin intolerant or as add-on therapy in those who are unable to reach the LDL-C goals despite being on statin therapy. This agent might not only exert lipid-lowering related benefits, but also favourable cardiometabolic effects.
authors.affiliation: Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Italy.
authors.forename: Dragana
authors.initials: D
authors.lastname: Nikolic
authors.affiliation: Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK.
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.affiliation: Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Davidson
authors.affiliation: Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, Italy.
authors.forename: Manfredi
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: Department of Hypertension, Chair of Nephrology and Hypertension, University of Lodz, Poland. Electronic address: maciejbanach@aol.co.uk.
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D008078:Cholesterol, LDL / Q000187:drug effects*; D017322:Clinical Trials, Phase II as Topic; D003998:Dicarboxylic Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology; D051379:Mice; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D051381:Rats
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D003998:Dicarboxylic Acids; D005227:Fatty Acids; D000960:Hypolipidemic Agents; C581236:8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid; D001275:ATP Citrate (pro-S)-Lyase; D055372:AMP-Activated Protein Kinases
keywords: Cardiometabolic risk; ETC-1002; Lipid lowering therapy; Low density lipoprotein cholesterol