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

Stem definitionDrug idCAS RN
endopeptidase inhibitors 5012 149709-62-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • sacubitril
  • AHU377
  • sucabitril
inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite and leads to increased levels of peptides that are degraded by neprilysin such as natriuretic peptides. It has been approved in combination with valsartan (under the name ENTRESTO) for the treatment of heart failure.
  • Molecular weight: 411.50
  • Formula: C24H29NO5
  • CLOGP: 4.47
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 92.70
  • ALOGS: -5.64
  • ROTB: 12
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.260 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 8.472 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 15.382 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 21.232 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 1.700 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 6.250 % High 1
herg hERG pIC50 4.775 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 39.355 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 11.967 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 2.130 % High 1
kinase-safety-class ACVR2A,ACVR2B,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,EIF2AK3,ERBB2,GRK2,ITK,MAPK7,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PIK3CG,PRKDC,TEK,TGFBR1 22
kinase-selectivity-class GRK2 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 7.079 High 1
mh-clint Mouse hepatocyte intrinsic clearance 147.911 High 1
mppb Mouse plasma protein binding (% unbound) 2.950 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 19.588 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 3.040 % High 1
rh-clint Rat hepatocyte intrinsic clearance 102.094 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 52.700 % High 1
rppb Rat plasma protein binding (% unbound) 1.800 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 901.571 uM High 1

Approvals:

DateAgencyCompanyOrphan
Nov. 19, 2015 EMA
July 7, 2015 FDA NOVARTIS PHARMS CORP
June 29, 2020 PMDA NOVARTIS PHARMA K.K.

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
Renal impairment 91.02 57.06 31 515 105390 90522511
Cardiac failure 89.87 57.06 31 515 109465 90518436
Muscle rupture 65.58 57.06 12 534 3129 90624772

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
Cardiac failure 160.81 47.34 71 1089 106785 42513390
Ventricular dysfunction 82.19 47.34 20 1140 4483 42615692
Cardiac failure chronic 80.47 47.34 23 1137 9578 42610597
Presyncope 76.28 47.34 27 1133 22360 42597815
Congestive cardiomyopathy 73.46 47.34 21 1139 8743 42611432
Angina pectoris 56.05 47.34 24 1136 32872 42587303
Hypotension 54.05 47.34 49 1111 257582 42362593
Fluid retention 53.64 47.34 23 1137 31596 42588579

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
Cardiac failure 254.26 45.17 100 1706 187526 110399967
Cardiac failure chronic 122.11 45.17 31 1775 13780 110573713
Hypotension 82.51 45.17 68 1738 523781 110063712
Ventricular dysfunction 77.03 45.17 19 1787 7492 110580001
Presyncope 76.20 45.17 29 1777 48858 110538635
Congestive cardiomyopathy 73.95 45.17 21 1785 14198 110573295
Renal impairment 73.92 45.17 43 1763 188402 110399091
Hyperkalaemia 61.32 45.17 34 1772 135762 110451731
Pulmonary oedema 53.22 45.17 28 1778 100631 110486862
Atrial fibrillation 51.76 45.17 37 1769 229605 110357888
Angina pectoris 49.87 45.17 23 1783 62272 110525221
Muscle rupture 49.37 45.17 12 1794 4448 110583045
Oedema peripheral 46.05 45.17 40 1766 328620 110258873

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C09DX04 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS
Angiotensin II receptor blockers (ARBs), other combinations
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35674 antihypertensive agent

Related Drugs by ATC class:

C09DX Angiotensin II receptor blockers (ARBs), other combinations 10 drugs
aliskirenamlodipinecandesartan cilexetilhydrochlorothiazideindapamideirbesartannebivolololmesartan medoxomiltelmisartanvalsartan

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

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Chronic heart failure indication 48447003




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.05 acidic
pKa2 12.4 acidic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
24MG;26MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9388134 Nov. 8, 2026 TREATMENT OF HEART FAILURE
49MG;51MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9388134 Nov. 8, 2026 TREATMENT OF HEART FAILURE
97MG;103MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9388134 Nov. 8, 2026 TREATMENT OF HEART FAILURE
15MG;16MG ENTRESTO SPRINKLE NOVARTIS N218591 April 12, 2024 RX CAPSULE, PELLETS ORAL 9388134 Nov. 8, 2026 TREATMENT OF HEART FAILURE
6MG;6MG ENTRESTO SPRINKLE NOVARTIS N218591 April 12, 2024 RX CAPSULE, PELLETS ORAL 9388134 Nov. 8, 2026 TREATMENT OF HEART FAILURE
24MG;26MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 11135192 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
24MG;26MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9517226 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
24MG;26MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9937143 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
49MG;51MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 11135192 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
49MG;51MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9517226 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
49MG;51MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9937143 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
97MG;103MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 11135192 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
97MG;103MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9517226 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
97MG;103MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 9937143 Aug. 22, 2033 TREATMENT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION
24MG;26MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 11058667 May 9, 2036 TREATING CHRONIC HEART FAILURE WITH REDUCED EJECTION FRACTION IN PATIENTS NOT TAKING AN ACE INHIBITOR OR AN ARB OR PREVIOUSLY TAKING LOW DOSES OF THESE AGENTS, BY TITRATING UP FROM HALF THE USUALLY RECOMMENDED STARTING DOSE
49MG;51MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 11058667 May 9, 2036 TREATING CHRONIC HEART FAILURE WITH REDUCED EJECTION FRACTION IN PATIENTS NOT TAKING AN ACE INHIBITOR OR AN ARB OR PREVIOUSLY TAKING LOW DOSES OF THESE AGENTS, BY TITRATING UP FROM HALF THE USUALLY RECOMMENDED STARTING DOSE
97MG;103MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 11058667 May 9, 2036 TREATING CHRONIC HEART FAILURE WITH REDUCED EJECTION FRACTION IN PATIENTS NOT TAKING AN ACE INHIBITOR OR AN ARB OR PREVIOUSLY TAKING LOW DOSES OF THESE AGENTS, BY TITRATING UP FROM HALF THE USUALLY RECOMMENDED STARTING DOSE
15MG;16MG ENTRESTO SPRINKLE NOVARTIS N218591 April 12, 2024 RX CAPSULE, PELLETS ORAL 10722471 Feb. 2, 2037 TREATMENT OF HEART FAILURE WITH ORAL PELLETS
6MG;6MG ENTRESTO SPRINKLE NOVARTIS N218591 April 12, 2024 RX CAPSULE, PELLETS ORAL 10722471 Feb. 2, 2037 TREATMENT OF HEART FAILURE WITH ORAL PELLETS

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Neprilysin Enzyme INHIBITOR IC50 8.22 CHEMBL DRUG LABEL
Neprilysin Enzyme IC50 8.30 CHEMBL

External reference:

IDSource
17ERJ0MKGI UNII
D10225 KEGG_DRUG
4034598 VUID
N0000191735 NUI
4034598 VANDF
C4033447 UMLSCUI
CHEBI:134714 CHEBI
6LD PDB_CHEM_ID
CHEMBL3137301 ChEMBL_ID
9811834 PUBCHEM_CID
DB09292 DRUGBANK_ID
9819 INN_ID
C000717211 MESH_SUPPLEMENTAL_RECORD_UI
7857 IUPHAR_LIGAND_ID
1656328 RXNORM
31106 MMSL
d08368 MMSL
016257 NDDF
716072000 SNOMEDCT_US
C4277755 UMLSCUI
D10226 KEGG_DRUG
CHEMBL417007 ChEMBL_ID
10430040 PUBCHEM_CID
C000609743 MESH_SUPPLEMENTAL_RECORD_UI
CHEBI:748213 CHEBI
17ERJ0MKGI INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0659 TABLET, FILM COATED 24 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0659 TABLET, FILM COATED 24 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0696 TABLET, FILM COATED 97 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0696 TABLET, FILM COATED 97 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0777 TABLET, FILM COATED 49 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0777 TABLET, FILM COATED 49 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-1231 PELLET 6 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-1231 PELLET 6 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-1238 PELLET 15 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-1238 PELLET 15 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-9659 TABLET, FILM COATED 24 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-9659 TABLET, FILM COATED 24 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-9777 TABLET, FILM COATED 49 mg ORAL NDA 35 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-9777 TABLET, FILM COATED 49 mg ORAL NDA 35 sections
Sacubitril and Valsartan Human Prescription Drug Label 2 0904-7580 TABLET, FILM COATED 24 mg ORAL ANDA 27 sections
Sacubitril and Valsartan Human Prescription Drug Label 2 0904-7581 TABLET, FILM COATED 97 mg ORAL ANDA 27 sections
Sacubitril and Valsartan Human Prescription Drug Label 2 0904-7582 TABLET, FILM COATED 49 mg ORAL ANDA 27 sections
sacubitril and valsartan HUMAN PRESCRIPTION DRUG LABEL 2 13668-634 TABLET 24 mg ORAL ANDA 19 sections
sacubitril and valsartan HUMAN PRESCRIPTION DRUG LABEL 2 13668-635 TABLET 49 mg ORAL ANDA 19 sections
sacubitril and valsartan HUMAN PRESCRIPTION DRUG LABEL 2 13668-636 TABLET 97 mg ORAL ANDA 19 sections
sacubitril and valsartan HUMAN PRESCRIPTION DRUG LABEL 2 13668-746 TABLET 49 mg ORAL ANDA 19 sections
sacubitril and valsartan HUMAN PRESCRIPTION DRUG LABEL 2 13668-747 TABLET 97 mg ORAL ANDA 19 sections
Sacubitril and valsartan HUMAN PRESCRIPTION DRUG LABEL 2 31722-673 TABLET, FILM COATED 24 mg ORAL ANDA 27 sections
Sacubitril and valsartan HUMAN PRESCRIPTION DRUG LABEL 2 31722-674 TABLET, FILM COATED 49 mg ORAL ANDA 27 sections
Sacubitril and valsartan HUMAN PRESCRIPTION DRUG LABEL 2 31722-675 TABLET, FILM COATED 97 mg ORAL ANDA 27 sections
Sacubitril and Valsartan Human Prescription Drug Label 2 33342-570 TABLET 24 mg ORAL ANDA 29 sections
Sacubitril and Valsartan Human Prescription Drug Label 2 33342-571 TABLET 49 mg ORAL ANDA 29 sections
Sacubitril and Valsartan Human Prescription Drug Label 2 33342-572 TABLET 97 mg ORAL ANDA 29 sections
Sacubitril and Valsartan Human Prescription Drug Label 2 42385-930 TABLET, FILM COATED 24 mg ORAL ANDA 29 sections
Sacubitril and Valsartan Human Prescription Drug Label 2 42385-931 TABLET, FILM COATED 49 mg ORAL ANDA 29 sections