Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:ETC-1002: a future option for lipid disorders? 2546 9

Despite major advances in pharmacologic therapy over the last few decades, dyslipidemia remains a prevalent, insufficiently recognized, and undercontrolled risk factor for cardiovascular disease. Statins are the mainstay of hypercholesterolemia treatment, but because of adherence and tolerability issues that limit dose titration, there is a need for additional therapies with good efficacy and better tolerability. Adenosine triphosphate (ATP) citrate lyase, a cytoplasmic enzyme responsible for the generation of acetyl coenzyme A for the de novo synthesis of fatty acids and cholesterol, is a very interesting molecular target for the reduction of plasma lipids. Furthermore, ATP citrate lyase inhibition may be accompanied by activation of 5'-adenosine monophosphate-activated protein kinase, a key signaling molecule that acts a central hub in cellular metabolic regulation. ETC-1002 is a small molecule inhibitor of ATP citrate lyase that also activates 5'-adenosine monophosphate-activated protein kinase, effectively reducing low-density lipoprotein cholesterol and inducing some other positive metabolic changes. Recent evidence from phase I and II clinical trials in humans has shown a positive efficacy and safety profile of ETC-1002, with low-density lipoprotein cholesterol reductions similar to those attainable by usual doses of many statins and with no major apparent side effects. These results potentially introduce a new family of medications that may expand our therapeutic arsenal against hypercholesterolemia.
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PMID:Adenosine triphosphate citrate lyase: Emerging target in the treatment of dyslipidemia. 2607 98