VALSARTAN DISODIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H27N5O3.2Na
Molecular Weight	479.4824
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[Na+].CCCCC(=O)N(CC1=CC=C(C=C1)C2=C(C=CC=C2)C3=NN=N[N-]3)[C@@H](C(C)C)C([O-])=O

InChI

InChIKey=SJSMGDIQKOTNND-IKXQUJFKSA-L

InChI=1S/C24H29N5O3.2Na/c1-4-5-10-21(30)29(22(16(2)3)24(31)32)15-17-11-13-18(14-12-17)19-8-6-7-9-20(19)23-25-27-28-26-23;;/h6-9,11-14,16,22H,4-5,10,15H2,1-3H3,(H2,25,26,27,28,31,32);;/q;2*+1/p-2/t22-;;/m0../s1

HIDE SMILES / InChI

Description
Sources: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/entresto.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/25052956http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/2009869

Valsartan (DIOVAN®) is a tetrazole derivative, and specific angiotensin II type 1 (AT1) receptor blocker that is indicated for the treatment of hypertension, to lower blood pressure. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme. Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan (DIOVAN®) blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Type-1 angiotensin II receptor 40 Target ID: CHEMBL227 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207620Orig1s000PharmR.pdf	Antagonist 2778	2.38 nM [Ki]
Neprilysin 29 Target ID: CHEMBL1944 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207620Orig1s000PharmR.pdf	Inhibitor 8297	2.3 nM [IC50]
Type-1 angiotensin II receptor 40 Target ID: CHEMBL227 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf	Blocker 537	2.43 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2578
Chronic heart failure with reduced ejection fraction 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207620Orig1s000lbl.pdf	Primary	Approved 8429	ENTRESTO Approved Use ENTRESTO is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker, indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB. Launch Date 2015
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf	Primary	Approved 8429	DIOVAN Approved Use Diovan is an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1) Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2) Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date 2011
Heart failure 103 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf	Primary	Approved 8429	DIOVAN Approved Use Diovan is an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1) Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2) Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date 2011
Myocardial infarction 121 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf	Palliative	Approved 8429	DIOVAN Approved Use Diovan is an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1) Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2) Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date 2011

C_max

Value	Dose	Analyte	Population
2808 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5756 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.141 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
20650 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
34310 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
22.56 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
8.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.55 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	VALSARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2.24 mg single, oral Overdose Dose: 2.24 mg Route: oral Route: single Dose: 2.24 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15222725	unknown, 25 years n = 1 Health Status: unknown Age Group: 25 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/15222725	Other AEs: Muscle cramps... Other AEs: Muscle cramps (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15222725
640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17762658	unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: https://pubmed.ncbi.nlm.nih.gov/17762658	Disc. AE: Hyperkalemia... Other AEs: Dizziness, Headache... AEs leading to discontinuation/dose reduction: Hyperkalemia (1 patient) Other AEs: Dizziness (8.3%) Headache (9.2%) Back pain (5.8%) Upper respiratory tract infection (5.8%) Nasopharyngitis (5%) Diarrhea (5%) Hypoglycemia (5%) Peripheral edema (4.2%) Nausea (4.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/17762658
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf https://pubmed.ncbi.nlm.nih.gov/15329835	pregnant Health Status: pregnant Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf https://pubmed.ncbi.nlm.nih.gov/15329835	Disc. AE: Disorder fetal... AEs leading to discontinuation/dose reduction: Disorder fetal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf https://pubmed.ncbi.nlm.nih.gov/15329835
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf	unhealthy n = 2316 Health Status: unhealthy Condition: hypertension Population Size: 2316 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf	Disc. AE: Headache, Dizziness... AEs leading to discontinuation/dose reduction: Headache (2.3%) Dizziness (2.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf	unhealthy n = 2506 Health Status: unhealthy Condition: Heart Failure Population Size: 2506 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf	Disc. AE: Creatinine increased, Potassium increased... AEs leading to discontinuation/dose reduction: Creatinine increased (0.5%) Potassium increased (0.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020665s039lbl.pdf

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9927	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9927
ChemicalBook	CB14657818	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB14657818
ChemicalBook	CB23133442	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB23133442
ChemicalBook	CB34813436	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB34813436
ChemicalBook	CB3952405	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3952405
ChemicalBook	CB6182539	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6182539
MolPort	MolPort-002-507-854	https://www.molport.com/shop/molecule-link/MolPort-002-507-854
MolPort	MolPort-003-666-608	https://www.molport.com/shop/molecule-link/MolPort-003-666-608
Selleck Chemicals	Valsartan(Diovan)	http://www.selleckchem.com/products/Valsartan(Diovan).html
ZINC	ZINC000003875259	http://zinc15.docking.org/substances/ZINC000003875259
eMolecules	1989469	https://www.emolecules.com/cgi-bin/more?vid=1989469
eMolecules	2724803	https://www.emolecules.com/cgi-bin/more?vid=2724803
eMolecules	32278148	https://www.emolecules.com/cgi-bin/more?vid=32278148
eMolecules	33507560	https://www.emolecules.com/cgi-bin/more?vid=33507560

PubMed

Title	Date	PubMed
Development and validation of chiral high-performance liquid chromatographic methods for the quantitation of valsartan and of the tosylate of valinebenzyl ester.	1996 Nov 8	8953194
Enantiomeric LC separation of valsartan on amylose based stationary phase.	2009 Aug	19746836
Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study.	2014 Apr	24446062
Determination of the R-enantiomer of valsartan in pharmaceutical formulation by capillary electrophoresis.	2015	25052956
LCZ696 : a new paradigm for the treatment of heart failure?	2015 Feb	25597387
Sacubitril/valsartan (LCZ696) for the treatment of heart failure.	2016	26642078
Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction.	2016 Aug	26990595
LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure.	2016 Jan	26280447

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose of ENTRESTO, previously known as LCZ696, is 49/51 mg (sacubitril/valsartan) twice-daily. Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg (sacubitril/valsartan) twice-daily, as tolerated by the patient.

Route of Administration: Oral

In Vitro Use Guide

30 nM to 1 uM valsartan (LCZ696 component) in the presence of 10 uM LBQ657 (Sacubitril (LCZ696 component) metabolite) demonstrate anti-fibrotic and anti-hypertrophic effects on rat cardiac fibroblasts and cardiomyocytes, respectively, cultured with 100 nM angiotensin II

Name

Type

Language

VALSARTAN DISODIUM

Common Name

English

L-VALINE, N-(1-OXOPENTYL)-N-((2'-(2H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-, SODIUM SALT (1:2)

Systematic Name

English

Code System Code Type Description

FDA UNII

U55M6YDH5T