Identification

Name
Sacubitril
Accession Number
DB09292
Type
Small Molecule
Groups
Approved
Description

Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. It was approved under the FDA's priority review process for use in heart failure on July 7, 2015.

Sacubitril's active metabolite, LBQ657 inhibits neprilysin, a neutral endopeptidase that would typically cleave natiuretic peptides such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP). ANP and BNP are released under atrial and ventricle stress, which activate downstream receptors leading to vasodilation, natriuresis and diuresis. Under normal conditions, neprilysin breaks down other vasodilating peptides and also vasoconstrictors such as angiotensin I and II, endothelin-1 and peptide amyloid beta-protein. Inhibition of neprilysin therefore leads to reduced breakdown and increased concentration of endogenous natriuretic peptides in addition to increased levels of vasoconstricting hormones such as angiotensin II.

Structure
Thumb
Synonyms
Not Available
External IDs
AHU-377 / AHU377 / LCZ-696 / LCZ696
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
EntrestoSacubitril (97 mg/1) + Valsartan (103 mg/1)Tablet, film coatedOralNovartis2015-07-07Not applicableUs
EntrestoSacubitril (24 mg) + Valsartan (26 mg)TabletOralNovartis2015-11-13Not applicableCanada
EntrestoSacubitril (24 mg) + Valsartan (26 mg)Tablet, film coatedOralNovartis Europharm Limited2015-11-19Not applicableEu
EntrestoSacubitril (97 mg) + Valsartan (103 mg)Tablet, film coatedOralNovartis Europharm Limited2015-11-19Not applicableEu
EntrestoSacubitril (24 mg) + Valsartan (26 mg)Tablet, film coatedOralNovartis Europharm Limited2015-11-19Not applicableEu
EntrestoSacubitril (49 mg) + Valsartan (51 mg)Tablet, film coatedOralNovartis Europharm Limited2015-11-19Not applicableEu
EntrestoSacubitril (24 mg) + Valsartan (26 mg)Tablet, film coatedOralNovartis Europharm Limited2015-11-19Not applicableEu
EntrestoSacubitril (49 mg) + Valsartan (51 mg)Tablet, film coatedOralNovartis Europharm Limited2015-11-19Not applicableEu
EntrestoSacubitril (97 mg) + Valsartan (103 mg)Tablet, film coatedOralNovartis Europharm Limited2015-11-19Not applicableEu
EntrestoSacubitril (49 mg) + Valsartan (51 mg)Tablet, film coatedOralNovartis Europharm Limited2015-11-19Not applicableEu
Categories
UNII
17ERJ0MKGI
CAS number
149709-62-6
Weight
Average: 411.498
Monoisotopic: 411.204573038
Chemical Formula
C24H29NO5
InChI Key
PYNXFZCZUAOOQC-UTKZUKDTSA-N
InChI
InChI=1S/C24H29NO5/c1-3-30-24(29)17(2)15-21(25-22(26)13-14-23(27)28)16-18-9-11-20(12-10-18)19-7-5-4-6-8-19/h4-12,17,21H,3,13-16H2,1-2H3,(H,25,26)(H,27,28)/t17-,21+/m1/s1
IUPAC Name
3-{[(2S,4R)-1-{[1,1'-biphenyl]-4-yl}-5-ethoxy-4-methyl-5-oxopentan-2-yl]carbamoyl}propanoic acid
SMILES
[H][[email protected]@](CC1=CC=C(C=C1)C1=CC=CC=C1)(C[[email protected]@]([H])(C)C(=O)OCC)NC(=O)CCC(O)=O

Pharmacology

Indication

Used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. It is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.

Structured Indications
Pharmacodynamics

n a 7-day valsartan-controlled study in patients with reduced ejection fraction (HFrEF), administration of sacubitril + valsartan (Entresto) resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP compared to valsartan. In a 21-day study in HFrEF patients, it significantly increased urine ANP and cGMP and plasma cGMP, and decreased plasma NT-proBNP, aldosterone and endothelin-1. In clinical studies, this combination had no effect on QTc interval.

Mechanism of action

Sacubitril's active metabolite, LBQ657 inhibits neprilysin, a neutral endopeptidase that would typically cleave natiuretic peptides, which includes: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP). ANP and BNP are released under atrial and ventricle stress, which activate downstream receptors leading to vasodilation, natriuresis and diuresis. Under normal conditions, neprilysin breaks down other vasodilating peptides and also vasoconstrictors such as angiotensin I and II, endothelin-1 and peptide amyloid beta-protein. Therefore, the inhibition of neprilysin leads to reduced breakdown and increased concentration of endogenous natriuretic peptides in addition to increased levels of vasoconstricting hormones such as angiotensin II. (However, when combined with valsartan, would result in blocking of angiotensin II to its receptor, preventing the vasoconstrictive effects and resulting in a decrease in vascular resistance and blood pressure.) Cardiovascular and renal effects of sacubitril is a result of the increased levels of peptides that are normally degraded by neprilysin.

TargetActionsOrganism
ANeprilysin
antagonist
inhibitor
Human
Absorption

Peak plasma concentrations of sacubitril and it's metabolite, LBQ657 are reached in 0.5 hours and 2 hours respectively. Food does not clinically affect the systemic exposure of sacubitril or LBQ657. The oral bioavailability of sacubitril is >60%. It should be noted that the valsartan found in this combination is more bioavailable than other market available valsartan.

Volume of distribution

103 L

Protein binding

Sacubitril and it's metabolite, LBQ657 are highly bound to plasma protein (94-97%).

Metabolism

Sacubitril is metabolized to LBQ657 by esterases. A low concentration (<10%) of a hydroxyl metabolite has been identified in plasma.

Route of elimination

52% to 68% of sacubitril (primarily as the active metabolite LBQ657) is excreted in urine. 37% to 48% of sacubitril (primarily as LBQ657) is excreted in feces

Half life

The half life of sacubitril is 1.1 to 3.6 hours, and the half life of it's metabolite LBQ657 is 9.9 to 11.1 hours.

Clearance
Not Available
Toxicity

The most common adverse reactions (≥5%) are hypotension, hyperkalemia, cough, dizziness, and renal failure.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcebutololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Acebutolol.Approved
AceclofenacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Aceclofenac.Approved, Investigational
AcemetacinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Acemetacin.Approved
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Acetylsalicylic acid.Approved, Vet Approved
AdapaleneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Adapalene.Approved
AlclofenacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Alclofenac.Approved, Withdrawn
AldesleukinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Aldesleukin.Approved
AliskirenAliskiren may increase the hyperkalemic activities of Sacubitril.Approved, Investigational
AlminoprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Alminoprofen.Experimental
AmifostineThe risk or severity of adverse effects can be increased when Amifostine is combined with Sacubitril.Approved, Investigational
AmilorideSacubitril may increase the hyperkalemic activities of Amiloride.Approved
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Sacubitril.Approved, Investigational
AmlodipineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Amlodipine.Approved
AmobarbitalAmobarbital may increase the hypotensive activities of Sacubitril.Approved, Illicit
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Sacubitril.Approved, Investigational
Amyl NitriteThe risk or severity of adverse effects can be increased when Sacubitril is combined with Amyl Nitrite.Approved
AndrographolideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Andrographolide.Investigational
AnisodamineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Anisodamine.Investigational
AntipyrineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Antipyrine.Approved
ApocyninThe risk or severity of adverse effects can be increased when Sacubitril is combined with Apocynin.Investigational
ApomorphineThe risk or severity of adverse effects can be increased when Apomorphine is combined with Sacubitril.Approved, Investigational
ApraclonidineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Apraclonidine.Approved
ApremilastThe risk or severity of adverse effects can be increased when Sacubitril is combined with Apremilast.Approved, Investigational
ArdeparinArdeparin may increase the hyperkalemic activities of Sacubitril.Approved, Investigational, Withdrawn
AripiprazoleAripiprazole may increase the hypotensive activities of Sacubitril.Approved, Investigational
ArotinololThe risk or severity of adverse effects can be increased when Arotinolol is combined with Sacubitril.Approved, Investigational
Arsenic trioxideThe risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Sacubitril.Approved, Investigational
AtenololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Atenolol.Approved
AzapropazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Azapropazone.Withdrawn
AzelastineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Azelastine.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Azilsartan medoxomil.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Balsalazide.Approved, Investigational
BarbexacloneBarbexaclone may increase the hypotensive activities of Sacubitril.Experimental
BarbitalBarbital may increase the hypotensive activities of Sacubitril.Illicit
BarnidipineThe risk or severity of adverse effects can be increased when Barnidipine is combined with Sacubitril.Approved
BemiparinBemiparin may increase the hyperkalemic activities of Sacubitril.Approved, Investigational
BenazeprilThe risk or severity of adverse effects can be increased when Benazepril is combined with Sacubitril.Approved, Investigational
BendazacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bendazac.Experimental
BendroflumethiazideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bendroflumethiazide.Approved
BenorilateThe risk or severity of adverse effects can be increased when Sacubitril is combined with Benorilate.Experimental
BenoxaprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Benoxaprofen.Withdrawn
BepridilThe risk or severity of adverse effects can be increased when Bepridil is combined with Sacubitril.Approved, Withdrawn
BetaxololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Betaxolol.Approved
BevoniumThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bevonium.Experimental
BisoprololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bisoprolol.Approved
BortezomibThe risk or severity of adverse effects can be increased when Bortezomib is combined with Sacubitril.Approved, Investigational
BretyliumThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bretylium.Approved
BrimonidineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Brimonidine.Approved
BromfenacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bromfenac.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Sacubitril.Approved, Investigational
BucillamineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bucillamine.Investigational
BufexamacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bufexamac.Experimental
BumadizoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bumadizone.Experimental
BumetanideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Bumetanide.Approved
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Sacubitril.Approved, Investigational
CanagliflozinCanagliflozin may increase the hyperkalemic activities of Sacubitril.Approved
Candesartan cilexetilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Candesartan.Approved
CandoxatrilThe risk or severity of adverse effects can be increased when Candoxatril is combined with Sacubitril.Experimental
CaptoprilThe risk or severity of adverse effects can be increased when Captopril is combined with Sacubitril.Approved
Carbaspirin calciumThe risk or severity of adverse effects can be increased when Sacubitril is combined with Carbaspirin calcium.Experimental, Investigational
CarbetocinThe risk or severity of adverse effects can be increased when Carbetocin is combined with Sacubitril.Approved
CarprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Carprofen.Approved, Vet Approved, Withdrawn
CarteololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Carteolol.Approved
CarvedilolThe risk or severity of adverse effects can be increased when Sacubitril is combined with Carvedilol.Approved, Investigational
CastanospermineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Castanospermine.Experimental
CelecoxibThe risk or severity of adverse effects can be increased when Sacubitril is combined with Celecoxib.Approved, Investigational
CertoparinCertoparin may increase the hyperkalemic activities of Sacubitril.Approved, Investigational
ChloroquineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Chloroquine.Approved, Vet Approved
ChlorothiazideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Chlorothiazide.Approved, Vet Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Sacubitril.Approved, Vet Approved
ChlorthalidoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Chlorthalidone.Approved
Choline magnesium trisalicylateThe risk or severity of adverse effects can be increased when Sacubitril is combined with Choline magnesium trisalicylate.Approved
CilazaprilThe risk or severity of adverse effects can be increased when Cilazapril is combined with Sacubitril.Approved
CilnidipineThe risk or severity of adverse effects can be increased when Cilnidipine is combined with Sacubitril.Approved, Investigational
CiprofloxacinSacubitril may increase the arrhythmogenic activities of Ciprofloxacin.Approved, Investigational
ClevidipineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Clevidipine.Approved
ClofarabineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Sacubitril.Approved, Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Sacubitril.Approved, Vet Approved
ClonidineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Clonidine.Approved
ClonixinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Clonixin.Approved
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Sacubitril.Approved
ConivaptanThe risk or severity of adverse effects can be increased when Conivaptan is combined with Sacubitril.Approved, Investigational
CurcuminThe risk or severity of adverse effects can be increased when Sacubitril is combined with Curcumin.Investigational
CyclosporineSacubitril may increase the hyperkalemic activities of Cyclosporine.Approved, Investigational, Vet Approved
D-LimoneneThe risk or severity of adverse effects can be increased when Sacubitril is combined with D-Limonene.Investigational
DalteparinDalteparin may increase the hyperkalemic activities of Sacubitril.Approved
DapagliflozinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Dapagliflozin.Approved
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Sacubitril.Investigational
DelaprilThe risk or severity of adverse effects can be increased when Delapril is combined with Sacubitril.Experimental
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Sacubitril.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Dexmedetomidine.Approved, Vet Approved
DiclofenacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Diclofenac.Approved, Vet Approved
DiclofenamideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Diclofenamide.Approved
DifenpiramideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Difenpiramide.Experimental
DiflunisalThe risk or severity of adverse effects can be increased when Sacubitril is combined with Diflunisal.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Sacubitril is combined with Diltiazem.Approved
DinutuximabThe risk or severity of adverse effects can be increased when Sacubitril is combined with Dinutuximab.Approved
DipyridamoleThe risk or severity of adverse effects can be increased when Sacubitril is combined with Dipyridamole.Approved
DoxazosinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Doxazosin.Approved
DrospirenoneSacubitril may increase the hyperkalemic activities of Drospirenone.Approved
DroxicamThe risk or severity of adverse effects can be increased when Sacubitril is combined with Droxicam.Approved
DuloxetineSacubitril may increase the orthostatic hypotensive activities of Duloxetine.Approved
DuvelisibThe risk or severity of adverse effects can be increased when Sacubitril is combined with Duvelisib.Investigational
E-6201The risk or severity of adverse effects can be increased when Sacubitril is combined with E-6201.Investigational
EfonidipineThe risk or severity of adverse effects can be increased when Efonidipine is combined with Sacubitril.Approved
EmpagliflozinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Empagliflozin.Approved
EnalaprilThe risk or severity of adverse effects can be increased when Enalapril is combined with Sacubitril.Approved, Vet Approved
EnalaprilatThe risk or severity of adverse effects can be increased when Enalaprilat is combined with Sacubitril.Approved
EnoxaparinEnoxaparin may increase the hyperkalemic activities of Sacubitril.Approved
EpirizoleThe risk or severity of adverse effects can be increased when Sacubitril is combined with Epirizole.Approved
EplerenoneEplerenone may increase the hyperkalemic activities of Sacubitril.Approved
EpoprostenolThe risk or severity of adverse effects can be increased when Epoprostenol is combined with Sacubitril.Approved
EprosartanThe risk or severity of adverse effects can be increased when Sacubitril is combined with Eprosartan.Approved
EsmololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Esmolol.Approved
Etacrynic acidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Etacrynic acid.Approved
EtanerceptThe risk or severity of adverse effects can be increased when Sacubitril is combined with Etanercept.Approved, Investigational
EthenzamideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Ethenzamide.Experimental
EtodolacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Etodolac.Approved, Investigational, Vet Approved
EtofenamateThe risk or severity of adverse effects can be increased when Sacubitril is combined with Etofenamate.Approved, Investigational
EtoricoxibThe risk or severity of adverse effects can be increased when Sacubitril is combined with Etoricoxib.Approved, Investigational
Evening primrose oilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Evening primrose oil.Approved, Investigational
exisulindThe risk or severity of adverse effects can be increased when Sacubitril is combined with exisulind.Investigational
FelbinacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Felbinac.Experimental
FelodipineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Felodipine.Approved, Investigational
FenbufenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Fenbufen.Approved
FenoldopamThe risk or severity of adverse effects can be increased when Fenoldopam is combined with Sacubitril.Approved
FenoprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Fenoprofen.Approved
FentiazacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Fentiazac.Experimental
FeprazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Feprazone.Experimental
Ferulic acidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Ferulic acid.Experimental
FimasartanThe risk or severity of adverse effects can be increased when Fimasartan is combined with Sacubitril.Approved, Investigational
FloctafenineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Floctafenine.Approved, Withdrawn
FlunixinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Flunixin.Vet Approved
FlunoxaprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Flunoxaprofen.Experimental
FlurbiprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Flurbiprofen.Approved, Investigational
FosinoprilThe risk or severity of adverse effects can be increased when Fosinopril is combined with Sacubitril.Approved
FurosemideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Furosemide.Approved, Vet Approved
GuacetisalThe risk or severity of adverse effects can be increased when Sacubitril is combined with Guacetisal.Experimental
GuanfacineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Guanfacine.Approved, Investigational
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Sacubitril.Approved, Vet Approved
HeparinHeparin may increase the hyperkalemic activities of Sacubitril.Approved, Investigational
HexobarbitalHexobarbital may increase the hypotensive activities of Sacubitril.Approved
HigenamineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Higenamine.Investigational
HydralazineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Hydralazine.Approved
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Hydrochlorothiazide.Approved, Vet Approved
HydroflumethiazideThe risk or severity of adverse effects can be increased when Hydroflumethiazide is combined with Sacubitril.Approved, Investigational
IbuprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Ibuprofen.Approved
IbuproxamThe risk or severity of adverse effects can be increased when Sacubitril is combined with Ibuproxam.Withdrawn
IcatibantThe risk or severity of adverse effects can be increased when Sacubitril is combined with Icatibant.Approved
IloprostThe risk or severity of adverse effects can be increased when Iloprost is combined with Sacubitril.Approved, Investigational
ImidaprilThe risk or severity of adverse effects can be increased when Imidapril is combined with Sacubitril.Investigational
Imidazole salicylateThe risk or severity of adverse effects can be increased when Sacubitril is combined with Imidazole salicylate.Experimental
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Sacubitril.Approved
IndapamideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Indapamide.Approved
IndobufenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Indobufen.Investigational
IndomethacinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Indomethacin.Approved, Investigational
IndoprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Indoprofen.Withdrawn
IndoraminThe risk or severity of adverse effects can be increased when Indoramin is combined with Sacubitril.Withdrawn
IrbesartanThe risk or severity of adverse effects can be increased when Sacubitril is combined with Irbesartan.Approved, Investigational
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Sacubitril.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Sacubitril.Approved, Vet Approved
Isosorbide DinitrateThe risk or severity of adverse effects can be increased when Sacubitril is combined with Isosorbide Dinitrate.Approved
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Sacubitril is combined with Isosorbide Mononitrate.Approved
IsoxicamThe risk or severity of adverse effects can be increased when Sacubitril is combined with Isoxicam.Withdrawn
IsoxsuprineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Isoxsuprine.Approved, Withdrawn
IsradipineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Isradipine.Approved
KebuzoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Kebuzone.Experimental
KetoprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Ketoprofen.Approved, Vet Approved
KetorolacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Ketorolac.Approved
LabetalolThe risk or severity of adverse effects can be increased when Sacubitril is combined with Labetalol.Approved
LacidipineThe risk or severity of adverse effects can be increased when Lacidipine is combined with Sacubitril.Approved, Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Leflunomide.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Sacubitril.Approved, Investigational
LevobunololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Levobunolol.Approved
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Sacubitril.Approved, Investigational
LevodopaSacubitril may increase the orthostatic hypotensive activities of Levodopa.Approved
LevosimendanThe risk or severity of adverse effects can be increased when Levosimendan is combined with Sacubitril.Approved, Investigational
LisinoprilThe risk or severity of adverse effects can be increased when Lisinopril is combined with Sacubitril.Approved, Investigational
LisofyllineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Lisofylline.Investigational
LithiumThe serum concentration of Lithium can be increased when it is combined with Sacubitril.Approved
LofexidineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Sacubitril.Approved, Investigational
LonazolacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Lonazolac.Experimental
LornoxicamThe risk or severity of adverse effects can be increased when Sacubitril is combined with Lornoxicam.Approved, Investigational
LosartanThe risk or severity of adverse effects can be increased when Sacubitril is combined with Losartan.Approved
LoxoprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Loxoprofen.Approved, Investigational
LumiracoxibThe risk or severity of adverse effects can be increased when Sacubitril is combined with Lumiracoxib.Approved, Investigational
Magnesium salicylateThe risk or severity of adverse effects can be increased when Sacubitril is combined with Magnesium salicylate.Approved
MannitolThe risk or severity of adverse effects can be increased when Sacubitril is combined with Mannitol.Approved, Investigational
MasoprocolThe risk or severity of adverse effects can be increased when Sacubitril is combined with Masoprocol.Approved, Investigational
MecamylamineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Mecamylamine.Approved
Meclofenamic acidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Meclofenamic acid.Approved, Vet Approved
Mefenamic acidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Mefenamic acid.Approved
MeloxicamThe risk or severity of adverse effects can be increased when Sacubitril is combined with Meloxicam.Approved, Vet Approved
MesalazineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Mesalazine.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Sacubitril is combined with Metamizole.Investigational, Withdrawn
MethazolamideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Methazolamide.Approved
MethohexitalMethohexital may increase the hypotensive activities of Sacubitril.Approved
MethyclothiazideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Methyclothiazide.Approved
MethyldopaThe risk or severity of adverse effects can be increased when Sacubitril is combined with Methyldopa.Approved
MethylphenobarbitalMethylphenobarbital may increase the hypotensive activities of Sacubitril.Approved
MetipranololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Metipranolol.Approved
MetolazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Metolazone.Approved
MetoprololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Metoprolol.Approved, Investigational
MinoxidilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Minoxidil.Approved
MizoribineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Mizoribine.Investigational
MoexiprilThe risk or severity of adverse effects can be increased when Moexipril is combined with Sacubitril.Approved
MofebutazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Mofebutazone.Experimental
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Sacubitril.Approved, Investigational
MoxonidineThe risk or severity of adverse effects can be increased when Moxonidine is combined with Sacubitril.Approved, Investigational
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Mycophenolate mofetil.Approved, Investigational
Mycophenolic acidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Mycophenolic acid.Approved
NabiloneThe risk or severity of adverse effects can be increased when Nabilone is combined with Sacubitril.Approved, Investigational
NabumetoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nabumetone.Approved
NadololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nadolol.Approved
NadroparinNadroparin may increase the hyperkalemic activities of Sacubitril.Approved
NafamostatThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nafamostat.Approved, Investigational
NaftifineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Naftifine.Approved
NaproxenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Naproxen.Approved, Vet Approved
NebivololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nebivolol.Approved, Investigational
NepafenacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nepafenac.Approved
NesiritideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nesiritide.Approved, Investigational
NicardipineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nicardipine.Approved
NicorandilNicorandil may increase the hyperkalemic activities of Sacubitril.Approved, Investigational
NifedipineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nifedipine.Approved
NifenazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nifenazone.Experimental
Niflumic AcidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Niflumic Acid.Approved
NilvadipineThe risk or severity of adverse effects can be increased when Nilvadipine is combined with Sacubitril.Approved, Investigational
NimesulideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nimodipine.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nisoldipine.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Nitrendipine is combined with Sacubitril.Approved, Investigational
Nitric OxideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Sacubitril.Approved
NitroaspirinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nitroaspirin.Investigational
NitroglycerinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nitroglycerin.Approved, Investigational
NitroprussideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Nitroprusside.Approved
ObinutuzumabThe risk or severity of adverse effects can be increased when Obinutuzumab is combined with Sacubitril.Approved
OlmesartanThe risk or severity of adverse effects can be increased when Sacubitril is combined with Olmesartan.Approved, Investigational
OlopatadineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Olopatadine.Approved
OlsalazineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Olsalazine.Approved
OmapatrilatThe risk or severity of adverse effects can be increased when Omapatrilat is combined with Sacubitril.Investigational
OrgoteinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Orgotein.Vet Approved
OxaprozinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Oxaprozin.Approved
OxprenololThe risk or severity of adverse effects can be increased when Oxprenolol is combined with Sacubitril.Approved
OxyphenbutazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Oxyphenbutazone.Approved, Withdrawn
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Sacubitril.Approved, Vet Approved
PapaverineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Papaverine.Approved
ParecoxibThe risk or severity of adverse effects can be increased when Sacubitril is combined with Parecoxib.Approved
ParnaparinParnaparin may increase the hyperkalemic activities of Sacubitril.Approved, Investigational
ParthenolideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Parthenolide.Investigational
PenbutololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Penbutolol.Approved, Investigational
PentobarbitalPentobarbital may increase the hypotensive activities of Sacubitril.Approved, Vet Approved
PerindoprilThe risk or severity of adverse effects can be increased when Perindopril is combined with Sacubitril.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Sacubitril.Approved
PhenobarbitalPhenobarbital may increase the hypotensive activities of Sacubitril.Approved
PhenoxybenzamineThe risk or severity of adverse effects can be increased when Phenoxybenzamine is combined with Sacubitril.Approved
PhentolamineThe risk or severity of adverse effects can be increased when Phentolamine is combined with Sacubitril.Approved
PhenylbutazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Phenylbutazone.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Sacubitril is combined with Pimecrolimus.Approved, Investigational
PindololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Pindolol.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Pipamperone is combined with Sacubitril.Approved, Investigational
PirfenidoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Pirfenidone.Approved, Investigational
PiroxicamThe risk or severity of adverse effects can be increased when Sacubitril is combined with Piroxicam.Approved, Investigational
PirprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Pirprofen.Experimental
PramipexoleThe risk or severity of adverse effects can be increased when Pramipexole is combined with Sacubitril.Approved, Investigational
PranoprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Pranoprofen.Experimental, Investigational
PrazosinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Prazosin.Approved
PrimidonePrimidone may increase the hypotensive activities of Sacubitril.Approved, Vet Approved
ProglumetacinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Proglumetacin.Experimental
PropacetamolThe risk or severity of adverse effects can be increased when Sacubitril is combined with Propacetamol.Approved, Investigational
PropofolThe risk or severity of adverse effects can be increased when Propofol is combined with Sacubitril.Approved, Investigational, Vet Approved
PropranololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Propranolol.Approved, Investigational
PropyphenazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Propyphenazone.Experimental
ProquazoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Proquazone.Experimental
PTC299The risk or severity of adverse effects can be increased when Sacubitril is combined with PTC299.Investigational
QuetiapineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Quetiapine.Approved
QuinaprilThe risk or severity of adverse effects can be increased when Quinapril is combined with Sacubitril.Approved, Investigational
RamiprilThe risk or severity of adverse effects can be increased when Ramipril is combined with Sacubitril.Approved
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Sacubitril.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Sacubitril.Approved
RescinnamineThe risk or severity of adverse effects can be increased when Rescinnamine is combined with Sacubitril.Approved
ReserpineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Reserpine.Approved, Investigational
ResveratrolThe risk or severity of adverse effects can be increased when Sacubitril is combined with Resveratrol.Approved, Experimental, Investigational
ReviparinReviparin may increase the hyperkalemic activities of Sacubitril.Approved, Investigational
RiociguatThe risk or severity of adverse effects can be increased when Sacubitril is combined with Riociguat.Approved
RisperidoneSacubitril may increase the hypotensive activities of Risperidone.Approved, Investigational
RofecoxibThe risk or severity of adverse effects can be increased when Sacubitril is combined with Rofecoxib.Investigational, Withdrawn
RopiniroleThe risk or severity of adverse effects can be increased when Ropinirole is combined with Sacubitril.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Ropivacaine is combined with Sacubitril.Approved
RotigotineThe risk or severity of adverse effects can be increased when Rotigotine is combined with Sacubitril.Approved
SalicylamideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Salicylamide.Approved
Salicylic acidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Salicylic acid.Approved, Vet Approved
SalsalateThe risk or severity of adverse effects can be increased when Sacubitril is combined with Salsalate.Approved
SecobarbitalSecobarbital may increase the hypotensive activities of Sacubitril.Approved, Vet Approved
SelegilineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Selegiline.Approved, Investigational, Vet Approved
SemapimodThe risk or severity of adverse effects can be increased when Sacubitril is combined with Semapimod.Investigational
SeratrodastThe risk or severity of adverse effects can be increased when Sacubitril is combined with Seratrodast.Approved
SerrapeptaseThe risk or severity of adverse effects can be increased when Sacubitril is combined with Serrapeptase.Investigational
SevofluraneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Sevoflurane.Approved, Vet Approved
Sodium NitriteThe risk or severity of adverse effects can be increased when Sacubitril is combined with Sodium Nitrite.Approved
Sodium phosphateSacubitril may increase the nephrotoxic activities of Sodium phosphate.Approved
SotalolThe risk or severity of adverse effects can be increased when Sacubitril is combined with Sotalol.Approved
SpiraprilThe risk or severity of adverse effects can be increased when Spirapril is combined with Sacubitril.Approved
SpironolactoneSacubitril may increase the hyperkalemic activities of Spironolactone.Approved
SRT501The risk or severity of adverse effects can be increased when Sacubitril is combined with SRT501.Investigational
StreptokinaseThe risk or severity of adverse effects can be increased when Sacubitril is combined with Streptokinase.Approved, Investigational
SufentanilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Sufentanil.Approved, Investigational
SulfasalazineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Sulfasalazine.Approved
SulindacThe risk or severity of adverse effects can be increased when Sacubitril is combined with Sulindac.Approved
SuprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Suprofen.Approved, Withdrawn
SuxibuzoneThe risk or severity of adverse effects can be increased when Sacubitril is combined with Suxibuzone.Experimental
TamsulosinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tamsulosin.Approved, Investigational
TarenflurbilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tarenflurbil.Investigational
TelmisartanThe risk or severity of adverse effects can be increased when Sacubitril is combined with Telmisartan.Approved, Investigational
TemocaprilThe risk or severity of adverse effects can be increased when Temocapril is combined with Sacubitril.Experimental, Investigational
TenidapThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tenidap.Experimental
TenoxicamThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tenoxicam.Approved
TepoxalinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tepoxalin.Vet Approved
TerazosinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Terazosin.Approved
TeriflunomideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Teriflunomide.Approved
ThalidomideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Thalidomide.Approved, Investigational, Withdrawn
ThiamylalThiamylal may increase the hypotensive activities of Sacubitril.Approved, Vet Approved
ThiopentalThiopental may increase the hypotensive activities of Sacubitril.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Thioridazine.Approved, Withdrawn
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tiaprofenic acid.Approved
TimololThe risk or severity of adverse effects can be increased when Sacubitril is combined with Timolol.Approved
TinoridineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tinoridine.Investigational
TinzaparinTinzaparin may increase the hyperkalemic activities of Sacubitril.Approved
TizanidineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tizanidine.Approved
TolazolineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tolazoline.Approved, Vet Approved
TolcaponeThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tolcapone.Approved, Withdrawn
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tolfenamic Acid.Approved
TolmetinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tolmetin.Approved
TolvaptanTolvaptan may increase the hyperkalemic activities of Sacubitril.Approved
TorasemideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Torasemide.Approved
TrandolaprilThe risk or severity of adverse effects can be increased when Trandolapril is combined with Sacubitril.Approved
TranilastThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tranilast.Approved, Investigational
TranylcypromineThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tranylcypromine.Approved
TretinoinThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tretinoin.Approved, Investigational, Nutraceutical
TriamtereneSacubitril may increase the hyperkalemic activities of Triamterene.Approved
TribenosideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tribenoside.Experimental
TrimethoprimTrimethoprim may increase the hyperkalemic activities of Sacubitril.Approved, Vet Approved
TriptolideThe risk or severity of adverse effects can be increased when Sacubitril is combined with Triptolide.Investigational
ValdecoxibThe risk or severity of adverse effects can be increased when Sacubitril is combined with Valdecoxib.Investigational, Withdrawn
ValsartanThe risk or severity of adverse effects can be increased when Sacubitril is combined with Valsartan.Approved, Investigational
VerapamilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Verapamil.Approved
ZaltoprofenThe risk or severity of adverse effects can be increased when Sacubitril is combined with Zaltoprofen.Approved, Investigational
ZileutonThe risk or severity of adverse effects can be increased when Sacubitril is combined with Zileuton.Approved, Investigational, Withdrawn
ZofenoprilThe risk or severity of adverse effects can be increased when Zofenopril is combined with Sacubitril.Experimental
ZomepiracThe risk or severity of adverse effects can be increased when Sacubitril is combined with Zomepirac.Withdrawn
Food Interactions
No interactions found.

References

General References
  1. Gu J, Noe A, Chandra P, Al-Fayoumi S, Ligueros-Saylan M, Sarangapani R, Maahs S, Ksander G, Rigel DF, Jeng AY, Lin TH, Zheng W, Dole WP: Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010 Apr;50(4):401-14. doi: 10.1177/0091270009343932. Epub 2009 Nov 23. [PubMed:19934029]
  2. Mills J, Vardeny O: The Role of Neprilysin Inhibitors in Cardiovascular Disease. Curr Heart Fail Rep. 2015 Dec;12(6):389-94. doi: 10.1007/s11897-015-0270-8. [PubMed:26466607]
  3. King JB, Bress AP, Reese AD, Munger MA: Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review. Pharmacotherapy. 2015 Sep;35(9):823-37. doi: 10.1002/phar.1629. [PubMed:26406774]
External Links
KEGG Drug
D10225
PubChem Compound
9811834
PubChem Substance
310265184
ChemSpider
7987587
ChEBI
134714
ChEMBL
CHEMBL3137301
PharmGKB
PA166131580
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sacubitril
ATC Codes
C09DX04 — Valsartan and sacubitril
FDA label
Download (1.28 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceMild and Moderate Renal Impairment1
2CompletedNot AvailableConcurrent Obesity / Hypertensive1
2CompletedNot AvailableHepatic Impairment1
2CompletedNot AvailableMild to Moderate Hypertension1
2CompletedNot AvailableSalt-sensitive Hypertension1
2CompletedTreatmentChronic Heart Failure (CHF)1
2CompletedTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
2CompletedTreatmentHeart Failure, Unspecified1
2CompletedTreatmentHypertension,Essential1
2CompletedTreatmentHypertensive5
2CompletedTreatmentSystolic Hypertension1
2RecruitingTreatmentDiastolic Dysfunction1
2RecruitingTreatmentPeripheral Arterial Disease (PAD)1
2, 3RecruitingTreatmentPediatric Heart Failure1
3Active Not RecruitingTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
3CompletedTreatmentHypertension With Renal Dysfunction1
3CompletedTreatmentHypertension,Essential4
3CompletedTreatmentHypertensive1
3CompletedTreatmentSevere Hypertension1
3RecruitingTreatmentAcute Myocardial Infarction (AMI)1
3RecruitingTreatmentChronic Heart Failure (CHF) / Heart Failure, Unspecified1
3RecruitingTreatmentChronic Heart Failure With Reduced Ejection Fraction (HFrEF)2
3RecruitingTreatmentHeart Failure With Preserved Ejection Fraction (HFpEF)2
3TerminatedTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
3WithdrawnTreatmentHypertensive1
4Active Not RecruitingSupportive CareHearth Failure With Reduced Ejection Fraction (HFrEF)1
4Active Not RecruitingTreatmentMitral Valve Insufficiency / Symptomatic left ventricular ejection fraction ≤ 35% Chronic heart failure1
4Not Yet RecruitingTreatmentCongestive Heart Failure (CHF) / Hypertensive1
4Not Yet RecruitingTreatmentHeart Failure, Unspecified1
4RecruitingNot AvailableHeart Failure With Reduced Ejection Fraction (HFrEF)1
4RecruitingOtherHeart Failure, Unspecified1
4RecruitingSupportive CareAcute Heart Failure (AHF)1
4RecruitingSupportive CareHeart Failure With Reduced Ejection Fraction (HFrEF)1
4RecruitingTreatmentBody Composition / Exercise Tolerance / Heart Failure, Unspecified / Strength, Muscle / Vasodilation1
4RecruitingTreatmentChronic Heart Failure With Reduced Ejection Fraction (HFrEF)1
4RecruitingTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
4RecruitingTreatmentHeart Failure, Unspecified3
Not AvailableAvailableNot AvailableHeart Failure With Reduced Ejection Fraction (HFrEF)1
Not AvailableRecruitingNot AvailableHeart Failure, Unspecified1
Not AvailableRecruitingOtherChronic Heart Failure (CHF) / Sleep Apnea Syndrome1
Not AvailableRecruitingTreatmentCongestive Heart Failure (CHF)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8796331No2003-01-142023-01-14Us
US8101659No2003-01-142023-01-14Us
US7468390No2003-11-272023-11-27Us
US8404744No2003-01-142023-01-14Us
US8877938No2007-05-272027-05-27Us
US9388134No2006-11-082026-11-08Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000942 mg/mLALOGPS
logP3.9ALOGPS
logP3.79ChemAxon
logS-5.6ALOGPS
pKa (Strongest Acidic)4.18ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.7 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity114.06 m3·mol-1ChemAxon
Polarizability45.41 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
Gamma amino acids and derivatives / Amphetamines and derivatives / Fatty acid esters / N-acyl amines / Dicarboxylic acids and derivatives / Secondary carboxylic acid amides / Carboxylic acid esters / Carboxylic acids / Organopnictogen compounds / Organonitrogen compounds
show 3 more
Substituents
Biphenyl / Gamma amino acid or derivatives / Amphetamine or derivatives / Fatty acid ester / Dicarboxylic acid or derivatives / Fatty amide / N-acyl-amine / Fatty acyl / Carboxylic acid ester / Carboxamide group
show 12 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Zinc ion binding
Specific Function
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptide...
Gene Name
MME
Uniprot ID
P08473
Uniprot Name
Neprilysin
Molecular Weight
85513.225 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Mills J, Vardeny O: The Role of Neprilysin Inhibitors in Cardiovascular Disease. Curr Heart Fail Rep. 2015 Dec;12(6):389-94. doi: 10.1007/s11897-015-0270-8. [PubMed:26466607]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Mills J, Vardeny O: The Role of Neprilysin Inhibitors in Cardiovascular Disease. Curr Heart Fail Rep. 2015 Dec;12(6):389-94. doi: 10.1007/s11897-015-0270-8. [PubMed:26466607]

Drug created on October 29, 2015 15:43 / Updated on November 09, 2017 04:48