U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H36O5
Molecular Weight 344.4861
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BEMPEDOIC ACID

SMILES

CC(C)(CCCCCC(O)CCCCCC(C)(C)C(O)=O)C(O)=O

InChI

InChIKey=HYHMLYSLQUKXKP-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description

Bempedoic acid (also known as ETC-1002) is a novel investigational drug being developed for the treatment of dyslipidemia, hypercholesterolemia and other cardio-metabolic risk factors. The hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose-lowering properties of ETC-1002, characterized in preclinical disease models, are believed to be due to dual inhibition of sterol and fatty acid synthesis and enhanced mitochondrial long-chain fatty acid β-oxidation. Investigations into the mechanism of action revealed that bempedoic acid-free acid activates AMP-activated protein kinase in a Ca(2+)/calmodulin-dependent kinase β-independent and liver kinase β-1-dependent manner, without detectable changes in adenylate energy charge. In the liver, bempedoic acid is also converted to a coenzyme A (CoA) derivative (ETC-1002-CoA )which directly inhibits ATP citrate lyase (ACL), a key enzyme that supplies a substrate for cholesterol and fatty acid synthesis in the liver. Inhibition of ACL by ETC-1002-CoA results in reduced cholesterol synthesis and upregulation of LDL receptor activity in the liver. This promotes the removal of LDL-C from the blood.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Primary
PubMed

PubMed

TitleDatePubMed
Cloning and expression of a human ATP-citrate lyase cDNA.
1992 Mar 1
Patents

Sample Use Guides

In Vivo Use Guide
ETC-1002 (BEMPEDOIC ACID) 180 mg tablets taken orally, once per day.
Route of Administration: Oral
In Vitro Use Guide
Consistent with ETC-1002-induced AMPK activation observed in rat liver, HepG2 cells treated with ETC-1002 (100 uM) revealed a sustained and concentration-dependent increase in AMPK (T172) and ACC (S79) phosphorylation comparable to the AMPK-activating effect of metformin (1,000 μM). To further characterize the mechanism leading to AMPK activation by ETC-1002, HepG2 cells were pretreated with STO-609, an AMPK kinase Ca2+/calmodulin-dependent kinase β (CaMKKβ)-specific inhibitor. STO-609 did not significantly reduce AMPK or ACC phosphorylation in ETC-1002- or metformin-treated cells, indicating that AMPK activation is not dependent on intracellular Ca2+ signaling. Intriguingly, while the ATP analog and AMPK inhibitor, compound C, significantly reduced AMPK and ACC phosphorylation by metformin, it did not inhibit ETC-1002-dependent AMPK activation. To determine whether ETC-1002-dependent AMPK activation is associated with reductions in AEC, intracellular ATP, ADP, and AMP concentrations were measured in HepG2 cells treated with vehicle, rotenone (10 μM), or ETC-1002 (100 μM). Treatment with rotenone (complex I inhibitor) resulted in increased AMP and ADP levels and in reduced ATP levels and AEC compared with vehicle treatment, while ETC-1002 had no effect. These data suggest that the activation of the AMPK pathway by ETC-1002 may be independent of reductions in energy production.
Name Type Language
BEMPEDOIC ACID
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
PENTADECANEDIOIC ACID, 8-HYDROXY-2,2,14,14-TETRAMETHYL-
Common Name English
8-HYDROXY-2,2,14,14-TETRAMETHYLPENTADECANEDIOIC ACID
Systematic Name English
ETC1002
Code English
BEMPEDOIC ACID [WHO-DD]
Common Name English
ETC-1002
Code English
ESP-55016
Code English
BEMPEDOIC ACID [USAN]
Common Name English
BEMPEDOIC ACID [INN]
Common Name English
Code System Code Type Description
PUBCHEM
10472693
Created by admin on Tue Oct 22 01:39:45 UTC 2019 , Edited by admin on Tue Oct 22 01:39:45 UTC 2019
PRIMARY
ChEMBL
CHEMBL3545313
Created by admin on Tue Oct 22 01:39:45 UTC 2019 , Edited by admin on Tue Oct 22 01:39:45 UTC 2019
PRIMARY
EVMPD
SUB183128
Created by admin on Tue Oct 22 01:39:45 UTC 2019 , Edited by admin on Tue Oct 22 01:39:45 UTC 2019
PRIMARY
CAS
738606-46-7
Created by admin on Tue Oct 22 01:39:45 UTC 2019 , Edited by admin on Tue Oct 22 01:39:45 UTC 2019
PRIMARY
INN
9891
Created by admin on Tue Oct 22 01:39:45 UTC 2019 , Edited by admin on Tue Oct 22 01:39:45 UTC 2019
PRIMARY