Bempedoic acid

Bempedoic acid
Clinical data
Other names	ESP-55016, ETC-1002
Routes of; administration	By mouth
ATC code	None;
Legal status
Legal status	Investigational;
Pharmacokinetic data
Elimination half-life	15–24 hrs[1]
Identifiers
	IUPAC name 8-Hydroxy-2,2,14,14-tetramethylpentadecanedioic acid;
CAS Number	738606-46-7;
PubChem CID	10472693;
IUPHAR/BPS	8321;
DrugBank	11936;
ChemSpider	8648104;
UNII	1EJ6Z6Q368;
KEGG	D10691;
ChEMBL	ChEMBL3545313;
ECHA InfoCard	100.238.679
Chemical and physical data
Formula	C19H36O5
Molar mass	344.492 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)(CCCCCC(CCCCCC(C)(C)C(=O)O)O)C(=O)O;
	InChI InChI=1S/C19H36O5/c1-18(2,16(21)22)13-9-5-7-11-15(20)12-8-6-10-14-19(3,4)17(23)24/h15,20H,5-14H2,1-4H3,(H,21,22)(H,23,24); Key:HYHMLYSLQUKXKP-UHFFFAOYSA-N;

Bempedoic acid is a drug under development by Esperion Therapeutics for the treatment of hypercholesterolemia.[2] In a study, it reduced LDL cholesterol by about 20 mg/dl compared to placebo and had no more side effects than placebo, although a higher percentage of drug receiving patients dropped out of the study because of side effects (11% vs. 7% under placebo).[3] As of March 2019, its effects on cardiovascular morbidity and mortality have not been determined; but studies are under way.[4]

Mechanism of action

Bempedoic acid is a prodrug. It is activated to the thioester with coenzyme A by the enzyme SLC27A2 in the liver.[1] The activated substance inhibits ATP citrate lyase, which is involved in the liver's biosynthesis of cholesterol upstream of HMG-CoA reductase, the enzyme that is blocked by statins.[3][4]

The substance also activates AMP-activated protein kinase, but this effect is likely not relevant in humans.[1]

Bempedoyl-CoA, the active metabolite. Coenzyme A is displayed in blue.

References

Bilen, Ozlem; Ballantyne, Christie M. (2016). "Bempedoic Acid (ETC-1002): An Investigational Inhibitor of ATP Citrate Lyase". Current Atherosclerosis Reports. 18 (10): 61. doi:10.1007/s11883-016-0611-4. PMC 5035316. PMID 27663902.
Clinical trial number NCT02988115 for "Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia and Statin Intolerant (CLEAR Serenity)" at ClinicalTrials.gov
Ray, Kausik K.; Bays, Harold E.; Catapano, Alberico L.; Lalwani, Narendra D.; Bloedon, Leanne T.; Sterling, Lulu R.; Robinson, Paula L.; Ballantyne, Christie M.; CLEAR Harmony Trial (2019). "Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol". New England Journal of Medicine. 380 (11): 1022–1032. doi:10.1056/NEJMoa1803917. PMID 30865796.
"Bempedoic Acid". Esperion Therapeutics. Retrieved 2019-03-15.

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[Bilen-1] Bilen, Ozlem; Ballantyne, Christie M. (2016). "Bempedoic Acid (ETC-1002): An Investigational Inhibitor of ATP Citrate Lyase". Current Atherosclerosis Reports. 18 (10): 61. doi:10.1007/s11883-016-0611-4. PMC 5035316. PMID 27663902.

[2] Clinical trial number NCT02988115 for "Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia and Statin Intolerant (CLEAR Serenity)" at ClinicalTrials.gov

[Ray-3] Ray, Kausik K.; Bays, Harold E.; Catapano, Alberico L.; Lalwani, Narendra D.; Bloedon, Leanne T.; Sterling, Lulu R.; Robinson, Paula L.; Ballantyne, Christie M.; CLEAR Harmony Trial (2019). "Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol". New England Journal of Medicine. 380 (11): 1022–1032. doi:10.1056/NEJMoa1803917. PMID 30865796.

[Esperion-4] "Bempedoic Acid". Esperion Therapeutics. Retrieved 2019-03-15.