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Details

Stereochemistry ACHIRAL
Molecular Formula C24H18N4O
Molecular Weight 378.4268
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GO-6976

SMILES

Cn1c2ccccc2c3c4c(CN=C4O)c5c6ccccc6n(CCC#N)c5c31

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

Molecular Formula C24H18N4O
Molecular Weight 378.4268
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Curator's Comment:: GO-6976 is CNS active in animals. No human data available.

Approval Year

PubMed

PubMed

TitleDatePubMed
Novel indolocarbazole protein kinase C inhibitors prevent reactivation of HIV-1 in latently infected cells.
1993 Dec
Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976.
1993 May 5
Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes.
1996 Aug 26
Oxidant-mediated activation of cytosolic phospholipase a(2) in pulmonary endothelium: role of protein kinase C alpha and a pertussis toxin-sensitive protein.
2005 May-Jun
Immunomodulatory drugs (IMiDs) increase the production of IL-2 from stimulated T cells by increasing PKC-theta activation and enhancing the DNA-binding activity of AP-1 but not NF-kappaB, OCT-1, or NF-AT.
2005 Oct
Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts.
2006 Dec
Regulation of skin microvasculature angiogenesis, cell migration, and permeability by a specific inhibitor of PKCalpha.
2006 Feb
Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways.
2006 Feb 1
Oxidative stress induces actin-cytoskeletal and tight-junctional alterations in hepatocytes by a Ca2+ -dependent, PKC-mediated mechanism: protective effect of PKA.
2006 Jun 1
Regulation of homocysteine-induced MMP-9 by ERK1/2 pathway.
2006 Mar
Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks.
2006 Sep
The sarcoplasmic-endoplasmic reticulum Ca2+ ATPase 2b regulates the Ca2+ transients elicited by P2Y2 activation in PC Cl3 thyroid cells.
2006 Sep
PKC inhibitor Go6976 induces mitosis and enhances doxorubicin-paclitaxel cytotoxicity in urinary bladder carcinoma cells.
2007 Aug 8
G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C.
2007 Jun
Ca(2+)-dependent protein kinase C isoforms are critical to estradiol 17beta-D-glucuronide-induced cholestasis in the rat.
2008 Dec
Phosphorylation of TRPV1 by neurokinin-1 receptor agonist exaggerates the capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons.
2008 Dec
Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes.
2008 Jun
Receptor-mediated tobacco toxicity: acceleration of sequential expression of alpha5 and alpha7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke.
2008 May
Inhibitory role of TGIF in the As2O3-regulated p21 WAF1/CIP1 expression.
2008 May
ADAM-10-mediated N-cadherin cleavage is protein kinase C-alpha dependent and promotes glioblastoma cell migration.
2009 Apr 8
Tamoxifen inhibits tumor cell invasion and metastasis in mouse melanoma through suppression of PKC/MEK/ERK and PKC/PI3K/Akt pathways.
2009 Jul 15
Lead acetate induces EGFR activation upstream of SFK and PKCalpha linkage to the Ras/Raf-1/ERK signaling.
2009 Mar 1
Alpha-adrenergic signalling activates protein kinase D and causes nuclear efflux of the transcriptional repressor HDAC5 in cultured adult mouse soleus skeletal muscle fibres.
2009 Mar 1
p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes.
2009 Mar 13
Regulation of secretases by all-trans-retinoic acid.
2009 May
Activation of ROS/NF-kappaB and Ca2+/CaM kinase II are necessary for VCAM-1 induction in IL-1beta-treated human tracheal smooth muscle cells.
2009 May 15
Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells: comparison with Toll-like receptor 4 responses in macrophages.
2010 Aug
Angiotensin II inhibits activity of human organic anion transporter 3 through activation of protein kinase Calpha: accelerating endocytosis of the transporter.
2010 Feb 10
Mechanisms of inhibition of T-type calcium current in the reticular thalamic neurons by 1-octanol: implication of the protein kinase C pathway.
2010 Jan
Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE(2) activation.
2010 Jan
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
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
Chk1 inhibitor Gö6976 enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy in vitro and in vivo.
2010 Nov 28
Phosphoinositide 3-kinase/protein kinase B signaling pathway is involved in estradiol 17β-D-glucuronide-induced cholestasis: complementarity with classical protein kinase C.
2010 Oct
Ursodeoxycholic acid is conjugated with taurine to promote secretin-stimulated biliary hydrocholeresis in the normal rat.
2011
Dual function of protein kinase C (PKC) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced manganese superoxide dismutase (MnSOD) expression: activation of CREB and FOXO3a by PKC-alpha phosphorylation and by PKC-mediated inactivation of Akt, respectively.
2011 Aug 26
A novel pathway responsible for lipopolysaccharide-induced translational regulation of TNF-α and IL-6 expression involves protein kinase C and fascin.
2011 Dec 15
Cardiac glycosides are potent inhibitors of interferon-β gene expression.
2011 Jan
Signaling cascades mediate astrocyte death induced by zinc.
2011 Jul 28
Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by piperine via the inhibition of PKCα/ERK1/2-dependent matrix metalloproteinase-9 expression.
2011 May 30
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
2011 Oct 30
Zinc-triggered induction of tissue plasminogen activator by brain-derived neurotrophic factor and metalloproteinases.
2011 Sep
Angiotensin II plays a critical role in alcohol-induced cardiac nitrative damage, cell death, remodeling, and cardiomyopathy in a protein kinase C/nicotinamide adenine dinucleotide phosphate oxidase-dependent manner.
2012 Apr 17
Cannabinoid-induced enhanced interaction and protein levels of serotonin 5-HT(2A) and dopamine D₂ receptors in rat prefrontal cortex.
2012 Oct
Phorbol ester-modulation of estrogenic genomic effects triggered by the environmental contaminant benzanthracene.
2012 Sep
NGF upregulates the plasminogen activation inhibitor-1 in neurons via the calcineurin/NFAT pathway and the Down syndrome-related proteins DYRK1A and RCAN1 attenuate this effect.
2013
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
2013 Apr 15
P-cresol induces disruption of cardiomyocyte adherens junctions.
2013 Apr 5
The C1 domain-targeted isophthalate derivative HMI-1b11 promotes neurite outgrowth and GAP-43 expression through PKCα activation in SH-SY5Y cells.
2013 Jul
Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules.
2014 Jan
Patents

Sample Use Guides

Unknown
Route of Administration: Other
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 01:15:09 UTC 2021
Edited
by admin
on Sat Jun 26 01:15:09 UTC 2021
Record UNII
B9IQO7JZ16
Record Status Validated (UNII)
Record Version
  • Download
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
Created by admin on Sat Jun 26 01:15:09 UTC 2021 , Edited by admin on Sat Jun 26 01:15:09 UTC 2021
PRIMARY
EPA CompTox
136194-77-9
Created by admin on Sat Jun 26 01:15:09 UTC 2021 , Edited by admin on Sat Jun 26 01:15:09 UTC 2021
PRIMARY
PUBCHEM
3501
Created by admin on Sat Jun 26 01:15:09 UTC 2021 , Edited by admin on Sat Jun 26 01:15:09 UTC 2021
PRIMARY
FDA UNII
B9IQO7JZ16
Created by admin on Sat Jun 26 01:15:09 UTC 2021 , Edited by admin on Sat Jun 26 01:15:09 UTC 2021
PRIMARY
Related Record Type Details
ACTIVE MOIETY