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

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 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
Novel indolocarbazole protein kinase C inhibitors prevent reactivation of HIV-1 in latently infected cells.	1993 Dec	8279816
Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976.	1993 May 5	8486620
Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes.	1996 Aug 26	8772178
Indolocarbazoles exhibit strong antiviral activity against human cytomegalovirus and are potent inhibitors of the pUL97 protein kinase.	2000 Oct	11080540
Role for phospholipase D in receptor-mediated endocytosis.	2001 Jan	11134345
Direct targeting of human cytomegalovirus protein kinase pUL97 by kinase inhibitors is a novel principle for antiviral therapy.	2002 May	11961255
Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity.	2003 Oct	14511371
Differential modulation of CaV2.3 Ca2+ channels by Galphaq/11-coupled muscarinic receptors.	2004 Feb	14742680
Expression of adhesion molecules by sphingosine 1-phosphate and histamine in endothelial cells.	2004 Feb 20	14975703
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
Enhancement of fibronectin fibrillogenesis and bone formation by basic fibroblast growth factor via protein kinase C-dependent pathway in rat osteoblasts.	2004 Sep	15322235
TIS21/BTG2/PC3 is expressed through PKC-delta pathway and inhibits binding of cyclin B1-Cdc2 and its activity, independent of p53 expression.	2004 Sep 10	15302583
Phospholipase D isozymes mediate epigallocatechin gallate-induced cyclooxygenase-2 expression in astrocyte cells.	2004 Sep 10	15210717
Gefitinib ("Iressa", ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells.	2005 Apr	15723263
Cigarette smoke extract increases C5a receptor expression in human bronchial epithelial cells.	2005 Jul	15843499
Hypotonic shock mediation by p38 MAPK, JNK, PKC, FAK, OSR1 and SPAK in osmosensing chloride secreting cells of killifish opercular epithelium.	2005 Mar	15767308
Aldose reductase pathway mediates JAK-STAT signaling: a novel axis in myocardial ischemic injury.	2005 May	15746188
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	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 Oct	16241859
Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts.	2006 Dec	17170093
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	16178010
Regulation of homocysteine-induced MMP-9 by ERK1/2 pathway.	2006 Mar	16251475
PKC inhibitor Go6976 induces mitosis and enhances doxorubicin-paclitaxel cytotoxicity in urinary bladder carcinoma cells.	2007 Aug 8	17320279
G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C.	2007 Jun	17374744
Inhibitory role of TGIF in the As2O3-regulated p21 WAF1/CIP1 expression.	2008 May	18210215
Tamoxifen inhibits tumor cell invasion and metastasis in mouse melanoma through suppression of PKC/MEK/ERK and PKC/PI3K/Akt pathways.	2009 Jul 15	19393235
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	19124542
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	20649597
Angiotensin II inhibits activity of human organic anion transporter 3 through activation of protein kinase Calpha: accelerating endocytosis of the transporter.	2010 Feb 10	19878671
Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE(2) activation.	2010 Jan	19804834
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
Chk1 inhibitor Gö6976 enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy in vitro and in vivo.	2010 Nov 28	20619533
Ursodeoxycholic acid is conjugated with taurine to promote secretin-stimulated biliary hydrocholeresis in the normal rat.	2011	22194894
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	22102721
Cardiac glycosides are potent inhibitors of interferon-β gene expression.	2011 Jan	21076398
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	21354279
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	22497828
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
P-cresol induces disruption of cardiomyocyte adherens junctions.	2013 Apr 5	23466501
The C1 domain-targeted isophthalate derivative HMI-1b11 promotes neurite outgrowth and GAP-43 expression through PKCα activation in SH-SY5Y cells.	2013 Jul	23643828

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 `Fri Dec 15 19:17:46 GMT 2023` Edited by `admin` on `Fri Dec 15 19:17:46 GMT 2023`
Record UNII	B9IQO7JZ16
Record Status	`Validated (UNII)`
Record Version