Go 6976
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Description: Potent protein kinase C inhibitor; selective for α and β isozymes
Chemical Name: 5,6,7,13-Tetrahydro-13-methyl-5-oxo-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-12-propanenitrile
Purity: ≥95%
Biological Activity
Go 6976 is a potent protein kinase C (PKC) inhibitor (IC50 = 7.9 nM). Discriminates between Ca2+-dependent and -independent isoforms of PKC in vitro; selectively inhibits PKCα and PKCβ1 (IC50 values are 2.3 and 6.2 nM respectively). Does not inhibit the activity of PKCδ, -ε, or -ζ (IC50 > 3μM). Also inhibits TrkA, TrkB, JAK2 and JAK3 tyrosine kinases (IC50 values are 5, 30, 130 and 370 nM respectively), PKCμ (PKD1) and the mitotic spindle checkpoint.Technical Data
M.Wt:
378.43
Formula:
C24H18N4O
Solubility:
Soluble to 10 mM in DMSO
Purity:
≥95%
Storage:
Store at -20°C
CAS No:
136194-77-9
The technical data provided above is for guidance only.
For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Background References
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Pharmacologic abrogation of the mitotic spindle checkpoint by an indolocarbazole discovered by cellular screening efficiently kills cancer cells.
Stolz A, Vogel C, Schneider V et al.
Cancer Res -
The expression of MMP-1 and MMP-9 is up-regulated by smooth muscle cells after their cross-talk with macrophages in high glucose conditions
RD Macarie, M Vadana, L Ciortan, MM Tucureanu, A Ciobanu, D Vinereanu, I Manduteanu, M Simionescu, E Butoi
J. Cell. Mol. Med., 2018;0(0):. -
ATM/ATR checkpoint activation downregulates CDC25C to prevent mitotic entry with uncapped telomeres.
EMBO J., 2012;31(16):3398-410. -
The NKG2D ligand ULBP2 is specifically regulated through an invariant chain-dependent endosomal pathway.
Uhlenbrock F, Hagemann-Jensen M, Kehlet S, Andresen L, Pastorekova S, Skov S
J Immunol, 2014;193(4):1654-65. -
Selective inhibition of protein kinase C isozymes by the indolocarbazole G� 6976
Martiny-Baron et al.
J.Biol.Chem., 1993;268:9194 -
Immunological demonstration of protein kinase Cμ in murine tissues and various cell lines.
Rennecke et al.
Eur.J.Biochem., 1996;242:428 -
Go 6976 is a potent inhibitor of neurotrophin-receptor intrinsic tyrosine kinase.
Behrens et al.
J.Neurochem., 1999;72:919 -
Go6976 is a potent inhibitor of JAK2 and FLT3 tyrosine kinases with significant activity in primary acute myeloid leukaemia cells.
Grandage et al.
Br.J.Haematol., 2006;135:303
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Citations for Go 6976
The citations listed below are publications that use Tocris products. Selected citations for Go 6976 include:
16 Citations: Showing 1 - 10
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Rapid exposure of macrophages to drugs resolves four classes of effects on the leading edge sensory pseudopod: Non-perturbing, adaptive, disruptive, and activating
Authors: Buckles Et al.
PLoS One 2020;15
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Autophagy is required for lung development and morphogenesis.
Authors: Yeganeh Et al.
J Clin Invest 2019;130:2904
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Organic barn dust inhibits surfactant protein D production through protein kinase-c alpha dependent increase of GPR116.
Authors: Schneberger Et al.
PLoS One 2018;13:e0208597
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PKC-α Triggers EGFR Ubiquitination, Endocytosis and ERK Activation in Podocytes Stimulated with High Glucose.
Authors: Lei Et al.
Cell Physiol Biochem 2017;42:281
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Protein kinase D at the Golgi controls NLRP3 inflammasome activation.
Authors: Zhang Et al.
J Exp Med 2017;214:2671
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Cancer cells that survive checkpoint adaptation contain micronuclei that harbor damaged DNA.
Authors: Lewis and Golsteyn
Cell Cycle 2016;15:3131
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Tyrosine Binding Protein Sites Regulate the Intracellular Trafficking and Processing of Amyloid Precursor Protein through a Novel Lysosome-Directed Pathway.
Authors: Tam Et al.
PLoS One 2016;11:e0161445
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P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest.
Authors: Shamseddine Et al.
Cell Death Dis 2015;6:e1947
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Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo.
Authors: Yuan Et al.
Sci Rep 2015;5:12889
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Targeting a cell state common to triple-negative breast cancers.
Authors: Muellner Et al.
J Biol Chem 2015;11:789
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Orexin-A promotes cell migration in cultured rat astrocytes via Ca2+-dependent PKCα and ERK1/2 signals.
Authors: Shu Et al.
PLoS One 2014;9:e95259
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Systematic analysis of bacterial effector-postsynaptic density 95/disc large/zonula occludens-1 (PDZ) domain interactions demonstrates Shigella OspE protein promotes protein kinase C activation via PDLIM proteins.
Authors: Yi Et al.
J Neurosci 2014;289:30101
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A ROCK Inhibitor Blocks the Inhibitory Effect of Chondroitin Sulfate Proteoglycan on Morphological Changes of Mesenchymal Stromal/Stem Cells into Neuron-Like Cells.
Authors: Lim and Joe
PLoS Biol 2013;21:447
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Raf kinase inhibitory protein is required for cerebellar long-term synaptic depression by mediating PKC-dependent MAPK activation.
Authors: Yamamoto Et al.
Biomol Ther (Seoul) 2012;32:14254
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Identification of small molecule inhibitors of phosphatidylinositol 3-kinase and autophagy.
Authors: Farkas Et al.
J Biol Chem 2011;286:38904
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Facilitation of long-term potentiation by muscarinic M(1) receptors is mediated by inhibition of SK channels.
Authors: Buchanan Et al.
Neuron 2010;68:948
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