CINACIGUAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C36H39NO5
Molecular Weight	565.6986
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CCCCN(CCC1=C(OCC2=CC=C(CCC3=CC=CC=C3)C=C2)C=CC=C1)CC4=CC=C(C=C4)C(O)=O

InChI

InChIKey=WPYWMXNXEZFMAK-UHFFFAOYSA-N

InChI=1S/C36H39NO5/c38-35(39)12-6-7-24-37(26-30-19-21-33(22-20-30)36(40)41)25-23-32-10-4-5-11-34(32)42-27-31-17-15-29(16-18-31)14-13-28-8-2-1-3-9-28/h1-5,8-11,15-22H,6-7,12-14,23-27H2,(H,38,39)(H,40,41)

HIDE SMILES / InChI

Molecular Formula	C36H39NO5
Molecular Weight	565.6986
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/25100108 | https://www.ncbi.nlm.nih.gov/pubmed/19406872 | https://www.ncbi.nlm.nih.gov/pubmed/18204474 | https://www.ncbi.nlm.nih.gov/pubmed/22778174

Cinaciguat acts specifically on oxidized/haem-free soluble guanylyl cyclase by binding to the enzyme's haem pocket and mimicking the nitric-oxide-bound haem group. It is in clinical development for the treatment of acute decompensated heart failure. Cinaciguat had been in phase II clinical trials. However, trials were terminated early because of an excess of hypotension in the cinaciguat arms and subsequent slow enrolment.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Soluble guanylate cyclase 22 Target ID: CHEMBL2111348 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20730699 \| http://www.pharmacodia.com/yaodu/html/v1/chemicals/5d28afa06a8e84b2c0a4cac2399f711d.html \| https://www.ncbi.nlm.nih.gov/pubmed/22162535	Activator 1404		15.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute decompensated heart failure 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22778174 https://www.ncbi.nlm.nih.gov/pubmed/22713287 https://www.ncbi.nlm.nih.gov/pubmed/19451356	Primary		Phase II 1133	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 22

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYPs 28	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/20730699/	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00C6VU	https://www.1pchem.com/search?query=1P00C6VU
1PlusChem LLC	1P00EMGY	https://www.1pchem.com/search?query=1P00EMGY
AK Scientific	3550AH	https://aksci.com/item_detail.php?cat=3550AH
ApexBio Technology	A3314	https://www.apexbt.com/catalogsearch/result/?q=A3314
Axon MedChem	2172	https://www.axonmedchem.com/product/2172
BLD Pharm	BD630649	http://www.bldpharm.com/search/Search.html?keyword=BD630649
Cayman Chemical	17468	http://www.caymanchem.com/app/template/Product.vm/catalog/17468
Chem Scene	CS-1169	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1169
Chem Scene	CS-6013	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-6013
MedChem Express	HY-14181	https://www.medchemexpress.com/search.html?q=HY-14181A&ft=&fa=&fp=
MedChem Express	HY-14181A	https://www.medchemexpress.com/search.html?q=HY-14181A&ft=&fa=&fp=
MolPort	MolPort-039-139-611	https://www.molport.com/shop/molecule-link/MolPort-039-139-611
MolPort	MolPort-042-665-825	https://www.molport.com/shop/molecule-link/MolPort-042-665-825
Molnova	M14089	https://www.molnova.com/en/serch-list.html?keywords=M14089
MuseChem	I004436	https://www.musechem.com/product/I004436.html
Ryan Scientific	101-94141	https://ryansci.com/products?q=101-94141&list_q=&search_type=exact
Ryan Scientific	KX1-004	https://ryansci.com/products?q=KX1-004&list_q=&search_type=exact
ShangHai Biochempartner	BCP000944	http://www.biochempartner.com/search_BCP000944
ShangHai Biochempartner	BCP07942	http://www.biochempartner.com/search_BCP07942
TargetMol	T1984	https://www.targetmol.com/search?keyword=T1984
eMolecules	300733083	https://orderbb.emolecules.com/search/#?query=300733083
eMolecules	44466495	https://orderbb.emolecules.com/search/#?query=44466495
eMolecules	45475576	https://orderbb.emolecules.com/search/#?query=45475576
mcule	MCULE-2336398228	https://mcule.com/MCULE-2336398228/
mcule	MCULE-6139644519	https://mcule.com/MCULE-6139644519/

PubMed

Title	Date	PubMed
Cinaciguat, a soluble guanylate cyclase activator, causes potent and sustained pulmonary vasodilation in the ovine fetus.	2009 Aug	19465519
Pharmacological activation of soluble guanylate cyclase protects the heart against ischemic injury.	2009 Aug 25	19667237
Role of guanylate cyclase modulators in decompensated heart failure.	2009 Dec	19568931
Gateways to clinical trials.	2009 Oct	19967103
Direct fusion of subunits of heterodimeric nitric oxide sensitive guanylyl cyclase leads to functional enzymes with preserved biochemical properties: evidence for isoform specific activation by ciguates.	2010 Dec 1	20797390
Nitric oxide sensitive guanylyl cyclase activity decreases during cerebral postnatal development because of a reduction in heterodimerization.	2010 Jan	19895661
Fluorescent fusion proteins of soluble guanylyl cyclase indicate proximity of the heme nitric oxide domain and catalytic domain.	2010 Jul 15	20657650
Structure of cinaciguat (BAY 58-2667) bound to Nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase.	2010 Jul 16	20463019
Cinaciguat, a soluble guanylate cyclase activator for the potential treatment of acute heart failure.	2010 Sep	20730699

Patents

Sample Use Guides

In Vivo Use Guide

25 ug/h, 10 ug/h during 48 h

Route of Administration: Intravenous

In Vitro Use Guide

Cinaciguat (1-50 nM) infused for 60 min starting 5 min before reperfusion significantly reduced infarction from 33.0 +/- 3.2% in control isolated rabbit hearts to 9.5-12.7% (P < 0.05).

Substance Class	Chemical Created by `admin` on `Fri Dec 16 19:33:10 UTC 2022` Edited by `admin` on `Fri Dec 16 19:33:10 UTC 2022`
Record UNII	59K0Y58UAD
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CINACIGUAT

Official Name

English

CINACIGUAT [JAN]

Common Name

English

cinaciguat [INN]

Common Name

English

BAY 58-2667

Code

English

Cinaciguat [WHO-DD]

Common Name

English

BAY-58-2667

Systematic Name

English

4-(((4-CARBOXYBUTYL)(2-(2-((4-(2-PHENYLETHYL)PHENYL)METHOXY)PHENYL)ETHYL)AMINO)METHYL)BENZOIC ACID

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29707