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=C3C(=O)NC5)C6=C(C=CC=C6)N4CCC#N

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	378.4259
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 21 Target ID: CHEMBL299 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8486620 \| https://www.ncbi.nlm.nih.gov/pubmed/7685108	Inhibitor 8504	2.3 nM [IC50]
Protein kinase C beta 22 Target ID: CHEMBL3045 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8486620 \| https://www.ncbi.nlm.nih.gov/pubmed/7685108	Inhibitor 8504	6.2 nM [IC50]
Tyrosine-protein kinase JAK2 59 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16956345	Inhibitor 8504
Tyrosine-protein kinase receptor FLT3 42 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16956345	Inhibitor 8504
Atrial natriuretic peptide receptor A 21 Target ID: CHEMBL1988 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21366551	Inhibitor 8504
Atrial natriuretic peptide receptor B 2 Target ID: CHEMBL2156 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21366551	Inhibitor 8504	380.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: http://adisinsight.springer.com/drugs/800011324	Primary		Preclinical	Unknown Approved Use Unknown
HIV-1 infection 156 Sources: http://adisinsight.springer.com/drugs/800011324	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules.	2014-01	24316436
The C1 domain-targeted isophthalate derivative HMI-1b11 promotes neurite outgrowth and GAP-43 expression through PKCα activation in SH-SY5Y cells.	2013-07	23643828
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013-04-15	23398362
P-cresol induces disruption of cardiomyocyte adherens junctions.	2013-04-05	23466501
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	23825664
Cannabinoid-induced enhanced interaction and protein levels of serotonin 5-HT(2A) and dopamine D₂ receptors in rat prefrontal cortex.	2012-10	22791651
Phorbol ester-modulation of estrogenic genomic effects triggered by the environmental contaminant benzanthracene.	2012-09	22643241
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.	2012-04-17	22497828
A novel pathway responsible for lipopolysaccharide-induced translational regulation of TNF-α and IL-6 expression involves protein kinase C and fascin.	2011-12-15	22102721
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011-10-30	22037377
Zinc-triggered induction of tissue plasminogen activator by brain-derived neurotrophic factor and metalloproteinases.	2011-09	21615740
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.	2011-08-26	21705328
Signaling cascades mediate astrocyte death induced by zinc.	2011-07-28	21575692
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.	2011-05-30	21354279
Cardiac glycosides are potent inhibitors of interferon-β gene expression.	2011-01	21076398
Ursodeoxycholic acid is conjugated with taurine to promote secretin-stimulated biliary hydrocholeresis in the normal rat.	2011	22194894
Chk1 inhibitor Gö6976 enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy in vitro and in vivo.	2010-11-28	20619533
Phosphoinositide 3-kinase/protein kinase B signaling pathway is involved in estradiol 17β-D-glucuronide-induced cholestasis: complementarity with classical protein kinase C.	2010-10	20815017
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.	2010-08	20649597
Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms.	2010-06-15	20152819
The effect of protein kinase C and G protein-coupled receptor kinase inhibition on tolerance induced by mu-opioid agonists of different efficacy.	2010-03	20008489
Angiotensin II inhibits activity of human organic anion transporter 3 through activation of protein kinase Calpha: accelerating endocytosis of the transporter.	2010-02-10	19878671
Mechanisms of inhibition of T-type calcium current in the reticular thalamic neurons by 1-octanol: implication of the protein kinase C pathway.	2010-01	19846748
Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE(2) activation.	2010-01	19804834
Tamoxifen inhibits tumor cell invasion and metastasis in mouse melanoma through suppression of PKC/MEK/ERK and PKC/PI3K/Akt pathways.	2009-07-15	19393235
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.	2009-05-15	19281832
Regulation of secretases by all-trans-retinoic acid.	2009-05	19476501
ADAM-10-mediated N-cadherin cleavage is protein kinase C-alpha dependent and promotes glioblastoma cell migration.	2009-04-08	19357285
p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes.	2009-03-13	19168439
Lead acetate induces EGFR activation upstream of SFK and PKCalpha linkage to the Ras/Raf-1/ERK signaling.	2009-03-01	19133285
Alpha-adrenergic signalling activates protein kinase D and causes nuclear efflux of the transcriptional repressor HDAC5 in cultured adult mouse soleus skeletal muscle fibres.	2009-03-01	19124542
Ca(2+)-dependent protein kinase C isoforms are critical to estradiol 17beta-D-glucuronide-induced cholestasis in the rat.	2008-12	18972403
Phosphorylation of TRPV1 by neurokinin-1 receptor agonist exaggerates the capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons.	2008-12	18809416
Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes.	2008-06	18357586
Receptor-mediated tobacco toxicity: acceleration of sequential expression of alpha5 and alpha7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke.	2008-05	18450646
Inhibitory role of TGIF in the As2O3-regulated p21 WAF1/CIP1 expression.	2008-05	18210215
PKC inhibitor Go6976 induces mitosis and enhances doxorubicin-paclitaxel cytotoxicity in urinary bladder carcinoma cells.	2007-08-08	17320279
G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C.	2007-06	17374744
Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts.	2006-12	17170093
Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks.	2006-09	18404483
The sarcoplasmic-endoplasmic reticulum Ca2+ ATPase 2b regulates the Ca2+ transients elicited by P2Y2 activation in PC Cl3 thyroid cells.	2006-09	17003265
Oxidative stress induces actin-cytoskeletal and tight-junctional alterations in hepatocytes by a Ca2+ -dependent, PKC-mediated mechanism: protective effect of PKA.	2006-06-01	16716901
Regulation of homocysteine-induced MMP-9 by ERK1/2 pathway.	2006-03	16251475
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.	2006-02-01	16178010
Regulation of skin microvasculature angiogenesis, cell migration, and permeability by a specific inhibitor of PKCalpha.	2006-02	16374459
Oxidant-mediated activation of cytosolic phospholipase a(2) in pulmonary endothelium: role of protein kinase C alpha and a pertussis toxin-sensitive protein.	2005-11-18	16291515
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.	2005-10	16241859
Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes.	1996-08-26	8772178
Novel indolocarbazole protein kinase C inhibitors prevent reactivation of HIV-1 in latently infected cells.	1993-12	8279816
Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976.	1993-05-05	8486620

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:42:47 GMT 2025` Edited by `admin` on `Mon Mar 31 19:42:47 GMT 2025`
Record UNII	B9IQO7JZ16
Record Status	`Validated (UNII)`
Record Version