GO-6976

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H18N4O
Molecular Weight	378.4259
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C2=C(C=CC=C2)C3=C1C4=C(C5=CC=CC=C5N4CCC#N)C6=C3C(=O)NC6

InChI

InChIKey=VWVYILCFSYNJHF-UHFFFAOYSA-N

InChI=1S/C24H18N4O/c1-27-17-9-4-2-7-14(17)20-21-16(13-26-24(21)29)19-15-8-3-5-10-18(15)28(12-6-11-25)23(19)22(20)27/h2-5,7-10H,6,12-13H2,1H3,(H,26,29)

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800011324
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8486620 | https://www.ncbi.nlm.nih.gov/pubmed/21366551 | https://www.ncbi.nlm.nih.gov/pubmed/16956345

Indolocarbazole GO-6976 inhibited the calcium-dependent protein kinase C (PKC) isozymes alpha and beta 1. As PKC is a central enzyme that modulates numerous biological functions GO-6976 is extensively used as a tool for studying the involvement of PKC in signal transduction pathways. GO6976 was originally synthesized by Goedecke (formerly a subsidiary of Warner-Lambert, now Pfizer) in Germany. Preclinical investigations carried out by Goedecke have been for the potential treatment of HIV infections. Preclinical research with GO 6976 had been conducted by Biomol Inc. and Calbiochem in the USA as a potential treatment for cancer. No further information has been available for the compound therefore it is assumed that development has been discontinued. In addition to GO-6976 inhibition of PKC, it was reported that GO-6976 also inhibits JAK 2 and FLT3 tyrosine kinases and non-kinase transmembrane guanylyl cyclase.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Protein kinase C alpha 20 Target ID: CHEMBL299 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8486620 \| https://www.ncbi.nlm.nih.gov/pubmed/7685108	Inhibitor 8297	2.3 nM [IC50]
Protein kinase C beta 21 Target ID: CHEMBL3045 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8486620 \| https://www.ncbi.nlm.nih.gov/pubmed/7685108	Inhibitor 8297	6.2 nM [IC50]
Tyrosine-protein kinase JAK2 55 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16956345	Inhibitor 8297
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16956345	Inhibitor 8297
Atrial natriuretic peptide receptor A 19 Target ID: CHEMBL1988 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21366551	Inhibitor 8297
Atrial natriuretic peptide receptor B 1 Target ID: CHEMBL2156 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21366551	Inhibitor 8297	380.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: http://adisinsight.springer.com/drugs/800011324	Primary		Preclinical	Unknown Approved Use Unknown
HIV-1 infection 151 Sources: http://adisinsight.springer.com/drugs/800011324	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Indolocarbazoles exhibit strong antiviral activity against human cytomegalovirus and are potent inhibitors of the pUL97 protein kinase.	2000 Oct	11080540
Ca(2+)-independent protein kinase C activity is required for alpha1-adrenergic-receptor-mediated regulation of ribosomal protein S6 kinases in adult cardiomyocytes.	2003 Jul 15	12720544
Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity.	2003 Oct	14511371
Phospholipase D is involved in oxidative stress-induced migration of vascular smooth muscle cells via tyrosine phosphorylation and protein kinase C.	2004 Apr 30	15150437
Differential modulation of CaV2.3 Ca2+ channels by Galphaq/11-coupled muscarinic receptors.	2004 Feb	14742680
Celecoxib simulates respiratory burst through pertussis toxin-sensitive G-protein, a possible signal for beta 2-integrin expression on human neutrophils.	2004 Jan 19	14729379
Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells.	2005 Apr	15723263
Isoflurane induces a protein kinase C alpha-dependent increase in cell-surface protein level and activity of glutamate transporter type 3.	2005 May	15709112
Transcriptional profiling of gamma delta T cells identifies a role for vitamin D in the immunoregulation of the V gamma 9V delta 2 response to phosphate-containing ligands.	2005 May 15	15879110
The sarcoplasmic-endoplasmic reticulum Ca2+ ATPase 2b regulates the Ca2+ transients elicited by P2Y2 activation in PC Cl3 thyroid cells.	2006 Sep	17003265
G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C.	2007 Jun	17374744
p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes.	2009 Mar 13	19168439
Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms.	2010 Jun 15	20152819
The effect of protein kinase C and G protein-coupled receptor kinase inhibition on tolerance induced by mu-opioid agonists of different efficacy.	2010 Mar	20008489
Cardiac glycosides are potent inhibitors of interferon-β gene expression.	2011 Jan	21076398
Cannabinoid-induced enhanced interaction and protein levels of serotonin 5-HT(2A) and dopamine D₂ receptors in rat prefrontal cortex.	2012 Oct	22791651
Phorbol ester-modulation of estrogenic genomic effects triggered by the environmental contaminant benzanthracene.	2012 Sep	22643241
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013 Apr 15	23398362

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Other

In Vitro Use Guide

Inflammation-induced multinucleation in cultured microglia was prevented by a protein kinase C (PKC) inhibitor GO-6976 (100 nM). Follicle-stimulating hormone (FSH ) significantly induced follicle-enclosed oocytes (FEOs) meiotic resumption, however, the induced effect of FSH was dose-dependently inhibited by Gö6976, and 100 nM Gö6976 completely blocked FSH function in oocyte meiotic resumption.

Name

Type

Language

GO-6976

Common Name

English

GOE-6976

Common Name

English

12H-INDOLO(2,3-A)PYRROLO(3,4-C)CARBAZOLE-12-PROPANENITRILE, 5,6,7,13-TETRAHYDRO-13-METHYL-5-OXO-

Systematic Name

English

Code System Code Type Description

CAS

136194-77-9