ZONIPORIDE MESYLATE HEMIHYDRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C17H16N6O.2CH4O3S.H2O
Molecular Weight	850.924
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of ZONIPORIDE MESYLATE HEMIHYDRATE

Structure Search

SMILES

O.CS(O)(=O)=O.CS(O)(=O)=O.NC(=N)NC(=O)C1=C(C2CC2)N(N=C1)C3=CC=CC4=NC=CC=C34.NC(=N)NC(=O)C5=C(C6CC6)N(N=C5)C7=CC=CC8=NC=CC=C78

InChI

InChIKey=HGNAEEHUNCEYEO-UHFFFAOYSA-N

InChI=1S/2C17H16N6O.2CH4O3S.H2O/c2*18-17(19)22-16(24)12-9-21-23(15(12)10-6-7-10)14-5-1-4-13-11(14)3-2-8-20-13;2*1-5(2,3)4;/h2*1-5,8-10H,6-7H2,(H4,18,19,22,24);2*1H3,(H,2,3,4);1H2

HIDE SMILES / InChI

Molecular Formula	C17H16N6O
Molecular Weight	320.3485
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	CH4O3S
Molecular Weight	96.106
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595915
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11259552 http://www.abcam.com/zoniporide-hydrochloride-ab142012.html

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium/hydrogen exchanger 2 9 Target ID: CHEMBL3133 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595915	Inhibitor 8297		12000.0 nM [IC50]
Sodium/hydrogen exchanger 1 12 Target ID: CHEMBL2781 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595915 \| https://www.ncbi.nlm.nih.gov/pubmed/12223226	Inhibitor 8297		14.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cardiovascular diseases 71 Sources: http://adisinsight.springer.com/drugs/800018057 https://www.ncbi.nlm.nih.gov/pubmed/12595915 https://www.ncbi.nlm.nih.gov/pubmed/11259552	Primary		Phase II 1132	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
0.07 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11277524	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ZONIPORIDE plasma	Rattus norvegicus population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11277524	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ZONIPORIDE plasma	Rattus norvegicus population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
46% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11277524	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ZONIPORIDE plasma	Rattus norvegicus population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	Disc. AE: Hepatic failure, Bilirubin elevated... Other AEs: Headache, Atrial fibrillation... AEs leading to discontinuation/dose reduction: Hepatic failure (0.8%) Bilirubin elevated Vomiting (25.6%) Other AEs: Headache (6.4%) Atrial fibrillation (6.4%) Tachycardia (10.9%) Jaundice (2.3%) Nausea (41.7%) Elevated liver enzyme levels Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573

AEs

AE	Significance	Dose	Population
Elevated liver enzyme levels		12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573
Hepatic failure	0.8% Disc. AE	12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573
Tachycardia	10.9%	12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573
Jaundice	2.3%	12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573
Vomiting	25.6% Disc. AE	12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573
Nausea	41.7%	12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573
Atrial fibrillation	6.4%	12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573
Headache	6.4%	12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573
Bilirubin elevated	Disc. AE	12 mg/kg 1 times / day multiple, intravenous Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573	unhealthy, ADULT n = 266 Health Status: unhealthy Condition: peripheral vascular disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 266 Sources: https://pubmed.ncbi.nlm.nih.gov/16202888 Page: p.573

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537 AO 16

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680395	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363680395	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680395	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680395	no
AO 16	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23046389/	yes [Km 3.4 uM]

PubMed

Title	Date	PubMed
Zoniporide: a potent and highly selective inhibitor of human Na(+)/H(+) exchanger-1.	2002 Sep 6	12223226
Efficacy of zoniporide, an Na/H exchange ion inhibitor, for reducing perioperative cardiovascular events in vascular surgery patients.	2005 Oct	16202888
Solute diffusion through stripped mouse duodenum.	2007 Dec	18195487
Targeting Na+/H+ exchanger regulation for cardiac protection: a RSKy approach?	2008 Apr	18222727
Paradoxical resistance to myocardial ischemia and age-related cardiomyopathy in NHE1 transgenic mice: a role for ER stress?	2009 Feb	19027022

Patents

Sample Use Guides

In Vivo Use Guide

Rabbits: 0.25, 1, and 4 mg/kg/h, i.v.

Route of Administration: Intravenous

In Vitro Use Guide

Zoniporide inhibited 22Na(+) uptake in fibroblasts expressing human NHE-1 in a concentration-dependent manner (IC(50) = 14 nM)

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:22:51 GMT 2023` Edited by `admin` on `Sat Dec 16 01:22:51 GMT 2023`
Record UNII	FW861BH5NA
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZONIPORIDE MESYLATE HEMIHYDRATE

Common Name

English

1H-PYRAZOLE-4-CARBOXAMIDE, N-(AMINOIMINOMETHYL)-5-CYCLOPROPYL-1-(5-QUINOLINYL)-, METHANESULFONATE, HYDRATE (2:2:1)

Common Name

English

Code System Code Type Description

PUBCHEM

71300877

Created by admin on Sat Dec 16 01:22:51 GMT 2023 , Edited by admin on Sat Dec 16 01:22:51 GMT 2023

PRIMARY

FDA UNII

FW861BH5NA

Created by admin on Sat Dec 16 01:22:51 GMT 2023 , Edited by admin on Sat Dec 16 01:22:51 GMT 2023

PRIMARY

EPA CompTox

DTXSID20187367

Created by admin on Sat Dec 16 01:22:51 GMT 2023 , Edited by admin on Sat Dec 16 01:22:51 GMT 2023

PRIMARY

CAS

336881-22-2

Created by admin on Sat Dec 16 01:22:51 GMT 2023 , Edited by admin on Sat Dec 16 01:22:51 GMT 2023

PRIMARY

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ZONIPORIDE

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					X4VP8104KI

ZONIPORIDE MESYLATE

ANHYDROUS->SOLVATE

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/12595915Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11259552 http://www.abcam.com/zoniporide-hydrochloride-ab142012.html

Originator

Approval Year

Targets

Conditions

Approved Use

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595915
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11259552 http://www.abcam.com/zoniporide-hydrochloride-ab142012.html

T_1/2

F_unbound

Drug as perpetrator