Description
ETC-1002 is a prodrug form of ETC-1002-CoA. ETC-1002 is conjugated to coenzyme A (CoA) by very long-chain acyl-CoA synthetase-1 (ACSVL1) to form ETC-1002-CoA, which inhibits ATP citrate lyase (K
i = 2 μM) and activates AMP-activated protein kinase (AMPK). ETC-1002 suppresses total lipid synthesis in wild-type and AMPKβ1 knockout primary murine hepatocytes.
In vivo, ETC-1002 (30 mg/kg) prevents increases in hepatic cholesterol and reduces the size of aortic atherosclerotic lesions induced by a high-fat high-cholesterol diet in
Apoe-/-/
Ampkβ1-/- (DKO) mice.
Description
Etc-1002 is a small molecule that can be used orally to lower LDL-C and is an activator of LIVER AMPK. ETC-1002 has an effective inhibitory effect on liver ATP-Citrate lyase.
Uses
ETC-1002 (Bempedoic acid, ESP-55016),also known as Bempedoic acid, is an orally available, once-daily LDL-C lowering small molecule designed to lower elevated levels of LDL-C and to avoid side effects associated with existing LDL-C lowering therapies.ETC-1002 is an activator of hepatic AMP-activated protein kinase (AMPK). It has potent inhibitory activity against hepatic ATP-citrate lyase(IC50=29 uM).
Definition
ChEBI: Bempedoic acid is an alpha,omega-dicarboxylic acid that is pentadecanedioic acid which is substituted by methyl groups groups at positions 2 and 14, and by a hydroxy group at position 8. It is a drug used for the treatment of high LDL cholesterol, which is sometimes referred to as 'bad cholesterol'. It has a role as an antilipemic drug, an EC 2.3.3.8 (ATP citrate synthase) inhibitor and a prodrug.
Indications
Bempedoic acid (ETC-1002) is a lipid-lowering agent approved by the FDA for use as an adjunct to maximally tolerated statin therapy for the reduction of LDL cholesterol, particularly in patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolaemia (HeFH).
brand name
NEXLETOL, NEXLIZET
Mechanism of action
Bempedoic acid (ETC-1002) inhibits cholesterol biosynthesis by inhibiting adenosine triphosphate-citrate lyase (ACL), which in turn inhibits cholesterol biosynthesis, leading to an increase in the expression of the LDL receptor and an enhancement of the plasma clearance of low-density lipoproteins (LDL-C). ETC-1002 is an orally active prodrug that is intracellularly activated. ETC-1002 activates AMPK, which in turn inhibits the production of pro-inflammatory cytokines and chemokines, and also contributes to the amelioration of diseases such as ASCVD and HeFH.
