CLAMIKALANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H22ClN3O5S2
Molecular Weight	471.978
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=S)NS(=O)(=O)C1=CC(CCNC(=O)C2=CC(Cl)=CC=C2OC)=CC=C1OC

InChI

InChIKey=VXTKXGKPBOLHRY-UHFFFAOYSA-N

InChI=1S/C19H22ClN3O5S2/c1-21-19(29)23-30(25,26)17-10-12(4-6-16(17)28-3)8-9-22-18(24)14-11-13(20)5-7-15(14)27-2/h4-7,10-11H,8-9H2,1-3H3,(H,22,24)(H2,21,23,29)

HIDE SMILES / InChI

Molecular Formula	C19H22ClN3O5S2
Molecular Weight	471.978
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/16047257
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18708091

The novel compounds clamikalant (HMR 1883) or its sodium salt HMR 1098) have been shown to block selectively Kir6.2/SUR1-composed K(ATP) channels. Clamikalant is under development by Aventis Pharma (formerly Hoechst Marion Roussel) for the potential treatment of heart arrest and ventricular arrhythmias. Nevertheless, clamikalant and its sodium salt did not pass the clinical trials

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sulfonylurea receptor 1, Kir6.2 13 Target ID: CHEMBL2096972 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21185839	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Arrhythmia 38 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15964023	Primary		Phase II 1132	Unknown Approved Use Unknown
Heart arrest 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15326916	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537 UGT1A9 380 UGT1A6 307 UGT2B7 389 UGT1A1 418

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680365	inconclusive [IC50 23.9185 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363680365	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680365	yes [IC50 6.7412 uM]

Drug as victim

Target	Modality	Activity
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12867491/	likely
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12867491/	likely
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12867491/	major [Km 82 uM]
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680365	no
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12867491/	yes [Km 233 uM]

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	3221AL	https://aksci.com/item_detail.php?cat=3221AL
Alfa Chemistry	ACM158751645	http://www.alfa-chemistry.com/search.aspx?q=ACM158751645
AstaTech	AB8954	http://astatechinc.com/CPSResult.php?CRNO=AB8954
Axon MedChem	1757	https://www.axonmedchem.com/product/1757
Combi-Blocks	QM-3713	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-3713
KeyOrganics	AS-44931	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-44931
MolPort	MolPort-039-333-566	https://www.molport.com/shop/molecule-link/MolPort-039-333-566
MolPort	MolPort-042-665-757	https://www.molport.com/shop/molecule-link/MolPort-042-665-757
MuseChem	M101552	https://www.musechem.com/product/M101552.html
eMolecules	300567871	https://orderbb.emolecules.com/search/#?query=300567871
eMolecules	50156504	https://orderbb.emolecules.com/search/#?query=50156504
eMolecules	50500432	https://orderbb.emolecules.com/search/#?query=50500432

PubMed

Title	Date	PubMed
Glucuronidation of HMR1098 in human microsomes: evidence for the involvement of UGT1A1 in the formation of S-glucuronides.	2003 Aug	12867491
Parstatin(1-26): the putative signal peptide of protease-activated receptor 1 confers potent protection from myocardial ischemia-reperfusion injury.	2010 Mar	20008957

Patents

Sample Use Guides

In Vivo Use Guide

in rats: 3 mg/kg i.v

Route of Administration: Intravenous

In Vitro Use Guide

HMR 1883 (Clamikalant) blocks KATPs in cardiac muscle cells with 10-50 fold higher potency than in pancreatic beta-cells and has little effect on the coronary vascular system. HMR 1883 has pharmacological selectivity for cardiac myocytes and thereby may be a promising substance for the prevention of ischemia-induced ventricular fibrillation. The rilmakalim-induced shortening of the APD90 in guinea pig right papillary muscle was antagonized half-maximally by HMR 1883 with 0.6 uM. The rilmakalim-induced shortening of the APD90 was half-maximally antagonized by HMR 1883 with 0.4 uM. The rilmakalim-induced whole-cell current (at 0 mV clamp-potential) was inhibited by HMR 1883 half-maximally 0.8 uM. Addition of HMR 1883 depolarized the cell potential half-maximally with concentrations of 20 uM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:05:10 GMT 2023` Edited by `admin` on `Fri Dec 15 16:05:10 GMT 2023`
Record UNII	94301K998R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CLAMIKALANT

Official Name

English

clamikalant [INN]

Common Name

English

HMR-1883

Code

English

1-((5-(2-(5-CHLORO-O-ANISAMIDO)ETHYL)-2-METHOXYPHENYL)SULFONYL)-3-METHYL-2-THIOUREA

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47793