Background:

Go 6976 is a selective inhibitor of PKC with IC50 value of 20 nM [1] [2].

Protein kinase C (PKC) is a family of protein kinase enzymes and plays an important role in controlling the function of other proteins by the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins [1-3].

Go 6976 is a potent PKC inhibitor and has a more potent activity with the reported PKC inhibitor H-7. When tested with nRT cells, Go 6976 showed a marked decrease the baseline T-current amplitude nearly 40% at the dose of 10 μM by inhibiting Ca2+-dependent PKC pathway [3]. In T cell lines ACH-2 and U1 infected with HIV-1, Go 6976 treatment effectively blocked viral transcription induced by Bryostain 1 or tumor necrosis factor α which lead to the inhibition of intracellular viral protein synthesis and viral shedding and also blocked IL-6 mediated posttranscriptional inducetion of viral protein [2].

It is also reported that Go 6976 is a potent inhibitor to EGFR and FLT3with IC50 value ranges from 0.033 nM to 3.3 μM and 0.7 nM, respectively [4] [5].

参考文献:
[1].  Gschwendt, M., et al., Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett, 1996. 392(2): p. 77-80.
[2].  Qatsha, K.A., et al., Go 6976, a selective inhibitor of protein kinase C, is a potent antagonist of human immunodeficiency virus 1 induction from latent/low-level-producing reservoir cells in vitro. Proc Natl Acad Sci U S A, 1993. 90(10): p. 4674-8.
[3].  Joksovic, P.M., et al., Mechanisms of inhibition of T-type calcium current in the reticular thalamic neurons by 1-octanol: implication of the protein kinase C pathway. Mol Pharmacol, 2010. 77(1): p. 87-94.
[4].  Taube, E., et al., A novel treatment strategy for EGFR mutant NSCLC with T790M-mediated acquired resistance. Int J Cancer, 2012. 131(4): p. 970-9.
[5].   Yoshida, A., et al., Go6976, a FLT3 kinase inhibitor, exerts potent cytotoxic activity against acute leukemia via inhibition of survivin and MCL-1. Biochem Pharmacol, 2014. 90(1): p. 16-24.