Go 6976是一种选择性的PKC抑制剂,IC50值为20 nM[1][2].

蛋白激酶C(PKC)属于蛋白激酶家族,通过对丝氨酸和苏氨酸残基上羟基的磷酸化作用,在控制其他蛋白功能中起着重要作用[1-3].

Go 6976是一种有效的PKC抑制剂,而且比已报道的PKC抑制剂H-7活性更强.当对nRT细胞测试时,Go 6976通过抑制Ca2+依赖性PKC通路,以10 μM的浓度明显减少了约40%的基线T-电流振幅[3].在HIV-1感染的T细胞系ACH-2和U1中,用Go 6976处理可有效地阻断Bryostain 1或肿瘤坏死因子α诱导的病毒转录,从而抑制细胞内病毒蛋白合成和病毒脱落,也可以阻断IL-6介导的转录后病毒蛋白诱导[2].

也有报道,Go 6976是一种有效的EGFR和FLT3抑制剂,IC50值范围分别是0.033 nM~3.3 μM和0.7 nM[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.