KN-62

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C38H35N5O6S2
Molecular Weight	721.844
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN([C@@H](CC1=CC=C(OS(=O)(=O)C2=CC=CC3=C2C=CN=C3)C=C1)C(=O)N4CCN(CC4)C5=CC=CC=C5)S(=O)(=O)C6=CC=CC7=C6C=CN=C7

InChI

InChIKey=RJVLFQBBRSMWHX-DHUJRADRSA-N

InChI=1S/C38H35N5O6S2/c1-41(50(45,46)36-11-5-7-29-26-39-19-17-33(29)36)35(38(44)43-23-21-42(22-24-43)31-9-3-2-4-10-31)25-28-13-15-32(16-14-28)49-51(47,48)37-12-6-8-30-27-40-20-18-34(30)37/h2-20,26-27,35H,21-25H2,1H3/t35-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C38H35N5O6S2
Molecular Weight	721.844
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2155222 | https://www.ncbi.nlm.nih.gov/pubmed/9720806

KN-62 (1-[N,O-Bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine) is an inhibitor of Ca2+/calmodulin-dependent protein kinase II (Ca2+/CaM kinase II). In addition, it acts as an antagonist of the P2X7 receptor.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) 1 Target ID: CHEMBL2111382 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2155222	Inhibitor 8297		0.9 µM [Ki]
P2X purinoceptor 7 12 Target ID: CHEMBL4805 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9113369 \| https://www.ncbi.nlm.nih.gov/pubmed/9720806	Antagonist 2778		15.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
Inhibition of sandfly fever Sicilian virus (Phlebovirus) replication in vitro by antiviral compounds.	1997 Sep-Oct	9403935
Effects of antagonists at the human recombinant P2X7 receptor.	1998 Jul	9720806
Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases.	2000 Apr 11	10737771
Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor.	2003 Sep 1	12815188
Extracellular zinc triggers ERK-dependent activation of Na+/H+ exchange in colonocytes mediated by the zinc-sensing receptor.	2004 Dec 10	15355987
Endothelin 1 and 3 enhance neuronal nitric oxide synthase activity through ETB receptors involving multiple signaling pathways in the rat anterior hypothalamus.	2004 Jul	15245872
Nuclear Ca2+ and CaM kinase IV specify hormonal- and Notch-responsiveness.	2005 Apr	15773917
Activation of CREB by tauroursodeoxycholic acid protects cholangiocytes from apoptosis induced by mTOR inhibition.	2005 Jun	15861431
Cocaine inhibition of GABA(A) current: role of dephosphorylation.	2006	17725511
CaMKII regulates retinoic acid receptor transcriptional activity and the differentiation of myeloid leukemia cells.	2007 May	17431504
Depolarization-induced differentiation of PC12 cells is mediated by phospholipase D2 through the transcription factor CREB pathway.	2008 Mar	18004999
Induction of nuclear receptors and drug resistance in the brain microvascular endothelial cells treated with antiepileptic drugs.	2008 May	18473823
Receptor-mediated tobacco toxicity: acceleration of sequential expression of alpha5 and alpha7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke.	2008 May	18450646
Plasticizer DBP Activates NLRP3 Inflammasome through the P2X7 Receptor in HepG2 and L02 Cells.	2016 Apr	26586371

Patents

Sample Use Guides

In Vivo Use Guide

Mice: 1 ug i.c.v.

Route of Administration: Other

In Vitro Use Guide

In hepatoma cells 1-5 uM KN-62 substantially reduced HIF-1α levels in a dose-dependent manner. In contrast to hepatoma cells, MCF7 (breast cancer) and SK-N-MC (neuroblastoma) cells did not respond to KN-62, even at high concentrations, which suggests that HIF-1α suppression by KN-62 is cancer type-dependent.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:05:06 GMT 2023` Edited by `admin` on `Fri Dec 15 18:05:06 GMT 2023`
Record UNII	63HM46XPOW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

KN-62

Common Name

English

KN 62

Common Name

English

5-ISOQUINOLINESULFONIC ACID, 4-((2S)-2-((5-ISOQUINOLINYLSULFONYL)METHYLAMINO)-3-OXO-3-(4-PHENYL-1-PIPERAZINYL)PROPYL)PHENYL ESTER

Systematic Name

English

Code System Code Type Description

FDA UNII

63HM46XPOW