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 18 Target ID: CHEMBL299 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8486620 \| https://www.ncbi.nlm.nih.gov/pubmed/7685108	Inhibitor 8146	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 8146	6.2 nM [IC50]
Tyrosine-protein kinase JAK2 53 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16956345	Inhibitor 8146
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16956345	Inhibitor 8146
Atrial natriuretic peptide receptor A 2 Target ID: CHEMBL1988 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21366551	Inhibitor 8146
Atrial natriuretic peptide receptor B 1 Target ID: CHEMBL2156 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21366551	Inhibitor 8146	380.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 581 Sources: http://adisinsight.springer.com/drugs/800011324	Primary		Preclinical	Unknown Approved Use Unknown
HIV-1 infection 145 Sources: http://adisinsight.springer.com/drugs/800011324	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Putative conventional protein kinase C inhibitor Gödecke 6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole] stimulates transglutaminase activity in primary mouse epidermal keratinocytes.	2002 Jul	12065737
Differential modulation of CaV2.3 Ca2+ channels by Galphaq/11-coupled muscarinic receptors.	2004 Feb	14742680
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
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
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	19281832
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
Zinc-triggered induction of tissue plasminogen activator by brain-derived neurotrophic factor and metalloproteinases.	2011 Sep	21615740
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013 Apr 15	23398362
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 `Sat Dec 17 02:31:05 UTC 2022` Edited by `admin` on `Sat Dec 17 02:31:05 UTC 2022`
Record UNII	B9IQO7JZ16
Record Status	`Validated (UNII)`
Record Version