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 8228	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 8228	6.2 nM [IC50]
Tyrosine-protein kinase JAK2 53 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16956345	Inhibitor 8228
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16956345	Inhibitor 8228
Atrial natriuretic peptide receptor A 2 Target ID: CHEMBL1988 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21366551	Inhibitor 8228
Atrial natriuretic peptide receptor B 1 Target ID: CHEMBL2156 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21366551	Inhibitor 8228	380.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 585 Sources: http://adisinsight.springer.com/drugs/800011324	Primary		Preclinical	Unknown Approved Use Unknown
HIV-1 infection 150 Sources: http://adisinsight.springer.com/drugs/800011324	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Role for phospholipase D in receptor-mediated endocytosis.	2001 Jan	11134345
Protein kinase C-dependent potentiation of intracellular calcium influx by sigma1 receptor agonists in rat hippocampal neurons.	2003 Nov	12975497
Effects of maribavir and selected indolocarbazoles on Epstein-Barr virus protein kinase BGLF4 and on viral lytic replication.	2004 May	15105156
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
Regulation of skin microvasculature angiogenesis, cell migration, and permeability by a specific inhibitor of PKCalpha.	2006 Feb	16374459
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
Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks.	2006 Sep	18404483
Phosphorylation of TRPV1 by neurokinin-1 receptor agonist exaggerates the capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons.	2008 Dec	18809416
Heme oxygenase-1 mediates the anti-inflammatory effect of Curcumin within LPS-stimulated human monocytes.	2008 Jun	18357586
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
Lead acetate induces EGFR activation upstream of SFK and PKCalpha linkage to the Ras/Raf-1/ERK signaling.	2009 Mar 1	19133285
p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes.	2009 Mar 13	19168439
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
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	21705328
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
Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules.	2014 Jan	24316436

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 `Thu Jul 06 02:24:59 UTC 2023` Edited by `admin` on `Thu Jul 06 02:24:59 UTC 2023`
Record UNII	B9IQO7JZ16
Record Status	`Validated (UNII)`
Record Version