bempedoic acid 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	5382	738606-46-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: bempedoic acid ETC-1002 ESP-55016 nexletol nilemdo	Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver. Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors Molecular weight: 344.49 Formula: C19H36O5 CLOGP: 3.95 LIPINSKI: 0 HAC: 5 HDO: 3 TPSA: 94.83 ALOGS: -4.21 ROTB: 14 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

bempedoic acid
ETC-1002
ESP-55016
nexletol
nilemdo

Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver. Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein receptors

Molecular weight: 344.49
Formula: C19H36O5
CLOGP: 3.95
LIPINSKI: 0
HAC: 5
HDO: 3
TPSA: 94.83
ALOGS: -4.21
ROTB: 14

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.18	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company	Orphan
April 1, 2020	EMA	FGK Representative Service GmbH
Feb. 21, 2020	FDA	ESPERION THERAPS INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Myalgia	209.74	52.58	69	501	146460	63341992

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Myalgia	129.96	85.71	41	247	84069	34872574

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Myalgia	235.35	56.45	78	575	185563	79558172
Blood creatine phosphokinase increased	60.41	56.45	22	631	66068	79677667

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	C10AX15	CARDIOVASCULAR SYSTEM LIPID MODIFYING AGENTS LIPID MODIFYING AGENTS, PLAIN Other lipid modifying agents
ATC	C10BA10	CARDIOVASCULAR SYSTEM LIPID MODIFYING AGENTS LIPID MODIFYING AGENTS, COMBINATIONS Combinations of various lipid modifying agents
MeSH PA	D000963	Antimetabolites
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D007004	Hypoglycemic Agents
MeSH PA	D000960	Hypolipidemic Agents
MeSH PA	D057847	Lipid Regulating Agents
FDA EPC	N0000193913	Adenosine Triphosphate-Citrate Lyase Inhibitor
FDA MoA	N0000193914	Adenosine Triphosphate-Citrate Lyase Inhibitors
CHEBI has role	CHEBI:35679	antilipemic drugs
CHEBI has role	CHEBI:50266	Prodrugs
CHEBI has role	CHEBI:149598	EC 2.3.3.8 (ATP citrate synthase) inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Atherosclerotic occlusive disease	indication	129573006
Familial hypercholesterolemia - heterozygous	indication	238079002

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.87	acidic
pKa2	5.47	acidic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
180MG	NEXLETOL	ESPERION THERAPS INC	N211616	Feb. 21, 2020	RX	TABLET	ORAL	10118881	Dec. 23, 2023	USE OF NEXLETOL AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG	NEXLETOL	ESPERION THERAPS INC	N211616	Feb. 21, 2020	RX	TABLET	ORAL	10941095	Dec. 23, 2023	USE OF NEXLETOL AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG	NEXLETOL	ESPERION THERAPS INC	N211616	Feb. 21, 2020	RX	TABLET	ORAL	8497301	Dec. 23, 2023	USE OF NEXLETOL AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG	NEXLETOL	ESPERION THERAPS INC	N211616	Feb. 21, 2020	RX	TABLET	ORAL	9000041	Dec. 23, 2023	USE OF NEXLETOL AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG	NEXLETOL	ESPERION THERAPS INC	N211616	Feb. 21, 2020	RX	TABLET	ORAL	9624152	Dec. 23, 2023	USE OF NEXLETOL AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY FOR INHIBITING CHOLESTEROL SYNTHESIS TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG;10MG	NEXLIZET	ESPERION THERAPS INC	N211617	Feb. 26, 2020	RX	TABLET	ORAL	10118881	Dec. 23, 2023	USE OF NEXLIZET AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG;10MG	NEXLIZET	ESPERION THERAPS INC	N211617	Feb. 26, 2020	RX	TABLET	ORAL	10941095	Dec. 23, 2023	USE OF NEXLIZET AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG;10MG	NEXLIZET	ESPERION THERAPS INC	N211617	Feb. 26, 2020	RX	TABLET	ORAL	8497301	Dec. 23, 2023	USE OF NEXLIZET AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG;10MG	NEXLIZET	ESPERION THERAPS INC	N211617	Feb. 26, 2020	RX	TABLET	ORAL	9000041	Dec. 23, 2023	USE OF NEXLIZET AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG;10MG	NEXLIZET	ESPERION THERAPS INC	N211617	Feb. 26, 2020	RX	TABLET	ORAL	9624152	Dec. 23, 2023	USE OF NEXLIZET AS AN ADJUNCT TO DIET AND MAXIMALLY TOLERATED STATIN THERAPY FOR INHIBITING CHOLESTEROL SYNTHESIS TO LOWER LDL-C IN ADULTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE
180MG;10MG	NEXLIZET	ESPERION THERAPS INC	N211617	Feb. 26, 2020	RX	TABLET	ORAL	10912751	March 14, 2036	A METHOD OF TREATING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE BY DECREASING THE LEVEL OF LDL-C USING A FIXED DOSE COMBINATION OF 180 MG BEMPEDOIC ACID AND 10 MG EZETIMIBE

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
180MG;10MG	NEXLIZET	ESPERION THERAPS INC	N211617	Feb. 26, 2020	RX	TABLET	ORAL	Feb. 26, 2023	NEW PRODUCT
180MG	NEXLETOL	ESPERION THERAPS INC	N211616	Feb. 21, 2020	RX	TABLET	ORAL	Feb. 21, 2025	NEW CHEMICAL ENTITY
180MG;10MG	NEXLIZET	ESPERION THERAPS INC	N211617	Feb. 26, 2020	RX	TABLET	ORAL	Feb. 21, 2025	NEW CHEMICAL ENTITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
ATP-citrate synthase	Enzyme	P53396	ACLY_HUMAN	INHIBITOR	Ki	5.69		SCIENTIFIC LITERATURE	DRUG LABEL

External reference:

ID	Source
1EJ6Z6Q368	UNII
C3659310	UMLSCUI
CHEBI:149601	CHEBI
CHEMBL3545313	ChEMBL_ID
10472693	PUBCHEM_CID
DB11936	DRUGBANK_ID
9891	INN_ID
C581236	MESH_SUPPLEMENTAL_RECORD_UI
D10691	KEGG_DRUG
8321	IUPHAR_LIGAND_ID
018287	NDDF
870523005	SNOMEDCT_US
870609002	SNOMEDCT_US
4039212	VANDF
2282403	RXNORM
331395	MMSL
38188	MMSL
d09518	MMSL

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Nexletol	HUMAN PRESCRIPTION DRUG LABEL	1	72426-118	TABLET, FILM COATED	180 mg	ORAL	NDA	31 sections
Nexletol	HUMAN PRESCRIPTION DRUG LABEL	1	72426-118	TABLET, FILM COATED	180 mg	ORAL	NDA	31 sections
Nexletol	HUMAN PRESCRIPTION DRUG LABEL	1	72426-118	TABLET, FILM COATED	180 mg	ORAL	NDA	31 sections
Nexlizet	HUMAN PRESCRIPTION DRUG LABEL	2	72426-818	TABLET, FILM COATED	180 mg	ORAL	NDA	31 sections
Nexlizet	HUMAN PRESCRIPTION DRUG LABEL	2	72426-818	TABLET, FILM COATED	180 mg	ORAL	NDA	31 sections
Nexlizet	HUMAN PRESCRIPTION DRUG LABEL	2	72426-818	TABLET, FILM COATED	180 mg	ORAL	NDA	31 sections