Bempedoic acid

Normally, LDL cholesterol is produced in the liver and circulates in the blood. When the blood becomes saturated, excess LDL deposits in blood vessels including the coronary arteries, increasing the risk of cardiovascular events.

Bempedoic acid is a prodrug that requires activation in the liver. The very-long-chain acyl-CoA synthetase-1 (ACSVL1) enzyme is responsible for its activation to ETC-1002-CoA, the pharmacologically active metabolite. ATP lyase (also known as ATP synthase) plays an important part of cholesterol synthesis. BETC-1002-CoA directly inhibits this enzyme after the parent drug is activated in the liver by coenzyme A (CoA).

This inhibition leads to upregulation of the LDL cholesterol receptor, reducing serum LDL-C via increased uptake and LDL clearance in the liver. By the above mechanisms, bempedoic acid causes a total decrease of circulating LDL-C that normally damages blood vessels and leads to atherosclerosis. Lastly, ETC-1002 activates AMP-activated protein kinase (AMPK) in rodents, which inhibits the synthesis of cholesterol via the inhibition of HMG-CoA reductase. The relevance of this to humans is unknown.