贝派度酸 (Nexletol, Nexlizet, Nilemdo +1)

概览

Bempedoic acid is a drug used in conjunction with lifestyle modification and/or other agents for the treatment of refractory hypercholesterolemia.

作用机制

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.

适应症

作为饮食和最大耐受性他汀类药物治疗的辅助药物，用于治疗患有杂合子家族性高胆固醇血症或需要额外降低LDL-C的动脉粥样硬化性心血管疾病的成人。

• Atherosclerotic Cardiovascular Diseases
• Heterozygous Familial Hypercholesterolemia (HeFH)