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

Stem definition	Drug id	CAS RN
endopeptidase inhibitors	5012	149709-62-6

Description:

Molecule	Description
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

Molecule

Description

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:

Date	Agency	Company
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 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
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 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
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:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (acidic/basic)
pKa1	4.05	acidic
pKa2	12.4	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
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 strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Neprilysin	Enzyme	P08473	NEP_HUMAN	INHIBITOR	IC50	8.22		CHEMBL	DRUG LABEL
Neprilysin	Enzyme		NEP_RAT		IC50	8.30		CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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