sacubitril 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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: ONP

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

Drug dosage:

None

ADMET properties:

None

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)

None

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 90.15 50.42 38 498 91210 34865185
Cardiac failure chronic 52.84 50.42 14 522 7865 34948530
Ventricular dysfunction 51.80 50.42 12 524 3893 34952502

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 126.65 45.27 52 865 154790 79588681
Cardiac failure chronic 71.33 45.27 18 899 11117 79732354
Ventricular dysfunction 50.01 45.27 12 905 6011 79737460
Hypotension 46.32 45.27 39 878 440278 79303193

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

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 8796331 Jan. 14, 2023 TREATMENT OF HEART FAILURE
49MG;51MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 8796331 Jan. 14, 2023 TREATMENT OF HEART FAILURE
97MG;103MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL 8796331 Jan. 14, 2023 TREATMENT OF HEART FAILURE
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
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

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
24MG;26MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL April 1, 2023 PEDIATRIC EXCLUSIVITY
49MG;51MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL April 1, 2023 PEDIATRIC EXCLUSIVITY
97MG;103MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL April 1, 2023 PEDIATRIC EXCLUSIVITY
24MG;26MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Feb. 16, 2024 LABELING REVISIONS RELATED TO CLINICAL STUDIES
49MG;51MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Feb. 16, 2024 LABELING REVISIONS RELATED TO CLINICAL STUDIES
97MG;103MG ENTRESTO NOVARTIS PHARMS CORP N207620 July 7, 2015 RX TABLET ORAL Feb. 16, 2024 LABELING REVISIONS RELATED TO CLINICAL STUDIES

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
C000609743 MESH_SUPPLEMENTAL_RECORD_UI
1656328 RXNORM
31106 MMSL
d08368 MMSL
016257 NDDF
716072000 SNOMEDCT_US
D10226 KEGG_DRUG
C4277755 UMLSCUI
CHEMBL417007 ChEMBL_ID
10430040 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0659 TABLET, FILM COATED 24 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0659 TABLET, FILM COATED 24 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0696 TABLET, FILM COATED 97 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0696 TABLET, FILM COATED 97 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0777 TABLET, FILM COATED 49 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-0777 TABLET, FILM COATED 49 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-9659 TABLET, FILM COATED 24 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-9659 TABLET, FILM COATED 24 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-9777 TABLET, FILM COATED 49 mg ORAL NDA 34 sections
ENTRESTO HUMAN PRESCRIPTION DRUG LABEL 2 0078-9777 TABLET, FILM COATED 49 mg ORAL NDA 34 sections