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

Stem definitionDrug idCAS RN
5382 738606-46-7

Description:

MoleculeDescription

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:

DoseUnitRoute
0.18 g O

ADMET properties:

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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,GRK2,IKBKB,ITK,JAK2,JAK3,MAP2K6,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPKAPK2,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PIK3CG,PIM2,PRKDC,SIK2,STK33,SYK,TEK,TGFBR1,ZAP70 41
kinase-selectivity-class AXL,CDK4,EIF2AK3,EPHB4,GRK2,INSR,MAP2K6,PLK1,PLK4,PTK2,STK33,TEK 12
pfas-class PFAS structural alert (1 = True, 0 = False) 0

Approvals:

DateAgencyCompanyOrphan
Feb. 21, 2020 FDA ESPERION THERAPS INC
April 1, 2020 EMA FGK Representative Service GmbH

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myalgia 426.26 37.76 147 1498 174978 90451824
Gout 99.00 37.76 28 1617 16831 90609971
Muscle spasms 89.69 37.76 56 1589 251827 90374975
Blood uric acid increased 60.06 37.76 16 1629 7688 90619114
Muscle rupture 52.29 37.76 12 1633 3129 90623673
Arthralgia 40.08 37.76 59 1586 778463 89848339
Blood uric acid abnormal 39.74 37.76 6 1639 156 90626646

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myalgia 272.71 62.47 102 1127 95978 42524128
Blood creatine phosphokinase increased 146.01 62.47 54 1175 48284 42571822

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myalgia 444.48 41.30 164 1963 222217 110364955
Blood creatine phosphokinase increased 148.77 41.30 55 2072 73022 110514150
Muscle rupture 111.44 41.30 24 2103 4436 110582736
Muscle spasms 108.61 41.30 67 2060 278090 110309082
Muscle discomfort 53.08 41.30 9 2118 465 110586707
Pain in extremity 46.92 41.30 52 2075 487066 110100106
Blood uric acid abnormal 46.73 41.30 8 2119 438 110586734
Dizziness 45.29 41.30 61 2066 698132 109889040

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
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 D000960 Hypolipidemic Agents
MeSH PA D000963 Antimetabolites
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D007004 Hypoglycemic 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:35526 hypoglycemic agent
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35679 antilipemic drug
CHEBI has role CHEBI:35821 anticholesteremic drug
CHEBI has role CHEBI:50266 prodrug
CHEBI has role CHEBI:145947 antiatherosclerotic agent
CHEBI has role CHEBI:149598 EC 2.3.3.8 (ATP citrate synthase) inhibitor

Related Drugs by ATC class:

C10AX Other lipid modifying agents 15 drugs
alipogene tiparvovecalirocumabdextrothyroxineevinacumabevolocumabezetimibeinclisiranlerodalcibep-ligalomitapidemeglutolmipomersenpolicosanol show all 15 →
C10BA Combinations of various lipid modifying agents 9 drugs
atorvastatinezetimibefenofibratelovastatinnicotinic acidpitavastatinpravastatinrosuvastatinsimvastatin

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

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (acidic/basic)
pKa1 4.87 acidic
pKa2 5.47 acidic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
180MG NEXLETOL ESPERION THERAPS INC N211616 Feb. 21, 2020 RX TABLET ORAL 11744816 March 14, 2036 A METHOD OF LOWERING LDL-C OR REDUCING THE RISK OF CARDIOVASCULAR DISEASE IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA USING 180 MG BEMPEDOIC ACID AND 10 MG EZETIMIBE
180MG;10MG NEXLIZET ESPERION THERAPS INC N211617 Feb. 26, 2020 RX TABLET ORAL 10912751 March 14, 2036 A METHOD OF LOWERING LDL-C OR REDUCING THE RISK OF CARDIOVASCULAR DISEASE IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA USING A FIXED-DOSE COMBINATION OF 180 MG BEMPEDOIC ACID AND 10 MG EZETIMIBE
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
180MG;10MG NEXLIZET ESPERION THERAPS INC N211617 Feb. 26, 2020 RX TABLET ORAL 11744816 March 14, 2036 A METHOD OF LOWERING LDL-C OR REDUCING THE RISK OF CARDIOVASCULAR DISEASE IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA USING 180 MG BEMPEDOIC ACID AND 10 MG EZETIMIBE
180MG;10MG NEXLIZET ESPERION THERAPS INC N211617 Feb. 26, 2020 RX TABLET ORAL 11744816 March 14, 2036 A METHOD OF TREATING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA OR ESTABLISHED ATHEROSCLEROTIC CARDIOVASCULAR DISEASE BY DECREASING THE LEVEL OF LDL-C USING 180 MG BEMPEDOIC ACID AND 10 MG EZETIMIBE
180MG NEXLETOL ESPERION THERAPS INC N211616 Feb. 21, 2020 RX TABLET ORAL 11926584 June 19, 2040 A METHOD OF LOWERING LOW-DENSITY LIPOPROTEIN CHOLESTEROL (LDL-C) IN A HUMAN PATIENT IN NEED THEREOF COMPRISING ADMINISTRATION OF BEMPEDOIC ACID ALONE OR IN COMBINATION WITH OTHER LIPID LOWERING THERAPIES
180MG NEXLETOL ESPERION THERAPS INC N211616 Feb. 21, 2020 RX TABLET ORAL 12404227 June 19, 2040 A METHOD OF TREATING PRIMARY HYPERLIPIDEMIA USING BEMPEDOIC ACID
180MG;10MG NEXLIZET ESPERION THERAPS INC N211617 Feb. 26, 2020 RX TABLET ORAL 11926584 June 19, 2040 A METHOD OF LOWERING LOW-DENSITY LIPOPROTEIN CHOLESTEROL (LDL-C) IN A HUMAN PATIENT IN NEED THEREOF COMPRISING ADMINISTRATION OF BEMPEDOIC ACID ALONE OR IN COMBINATION WITH OTHER LIPID LOWERING THERAPIES
180MG;10MG NEXLIZET ESPERION THERAPS INC N211617 Feb. 26, 2020 RX TABLET ORAL 12404227 June 19, 2040 A METHOD OF TREATING PRIMARY HYPERLIPIDEMIA USING BEMPEDOIC ACID

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
180MG NEXLETOL ESPERION THERAPS INC N211616 Feb. 21, 2020 RX TABLET ORAL March 22, 2027 EXPANDED INDICATION FOR USE AS AN ADJUNCT TO DIET, IN COMBINATION WITH OTHER LOW-DENSITY LIPOPROTEIN CHOLESTEROL (LDL-C) LOWERING THERAPIES, OR ALONE WHEN CONCOMITANT LDL-C LOWERING THERAPY IS NOT POSSIBLE, TO REDUCE LDL-C IN ADULTS WITH PRIMARY HYPERLIPIDEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH)
180MG NEXLETOL ESPERION THERAPS INC N211616 Feb. 21, 2020 RX TABLET ORAL March 22, 2027 TO REDUCE THE RISK OF MYOCARDIAL INFARCTION AND CORONARY REVASCULARIZATION IN ADULTS WHO ARE UNABLE TO TAKE RECOMMENDED STATIN THERAPY (INCLUDING THOSE NOT TAKING A STATIN) WITH ESTABLISHED CARDIOVASCULAR DISEASE (CVD), OR AT HIGH RISK FOR A CVD EVENT BUT WITHOUT ESTABLISHED CVD
180MG;10MG NEXLIZET ESPERION THERAPS INC N211617 Feb. 26, 2020 RX TABLET ORAL March 22, 2027 EXPANDED INDICATION FOR USE AS AN ADJUNCT TO DIET, ALONE OR IN COMBINATION WITH OTHER LDL-C LOWERING THERAPIES, TO REDUCE LDL-C IN ADULTS WITH PRIMARY HYPERLIPIDEMIA, INCLUDING HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH)
180MG;10MG NEXLIZET ESPERION THERAPS INC N211617 Feb. 26, 2020 RX TABLET ORAL March 22, 2027 TO REDUCE THE RISK OF MYOCARDIAL INFARCTION AND CORONARY REVASCULARIZATION IN ADULTS WHO ARE UNABLE TO TAKE RECOMMENDED STATIN THERAPY (INCLUDING THOSE NOT TAKING A STATIN) WITH ESTABLISHED CARDIOVASCULAR DISEASE (CVD), OR AT HIGH RISK FOR A CVD EVENT BUT WITHOUT ESTABLISHED CVD

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
ATP-citrate synthase Enzyme INHIBITOR Ki 5.69 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

IDSource
1EJ6Z6Q368 UNII
4039212 VANDF
C3659310 UMLSCUI
CHEBI:149601 CHEBI
A1JTY PDB_CHEM_ID
CHEMBL3545313 ChEMBL_ID
10472693 PUBCHEM_CID
DB11936 DRUGBANK_ID
9891 INN_ID
C581236 MESH_SUPPLEMENTAL_RECORD_UI
D10691 KEGG_DRUG
8321 IUPHAR_LIGAND_ID
870523005 SNOMEDCT_US
870609002 SNOMEDCT_US
331395 MMSL
38188 MMSL
d09518 MMSL
018287 NDDF
2282403 RXNORM
1EJ6Z6Q368 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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