Uses
Go 6976 is a potent FLT3 inihibtor which is been shown to initiate cytotoxicity involving acute leukemia. Also known as a PKC inhibitor, which results into apoptosis and tumor destruction. Cancer therapeutic agent.
Biological Activity
Potent protein kinase C (PKC) inhibitor (IC 50 = 7.9 nM). In vitro, discriminates between Ca 2+ -dependent and -independent isoforms of PKC; selectively inhibits PKC α and PKC β 1 (IC 50 values are 2.3 and 6.2 nM respectively) but does not inhibit the activity of PKC δ , - ε , or - ζ (IC 50 > 3 μ M). Also inhibits TrkA, TrkB, JAK2 and JAK3 tyrosine kinases (IC 50 values are 5, 30, 130 and 370 nM respectively).
Background
Gö6976 is an ATP-competitive PKC inhibitor specific for Ca2+-dependent PKCα and PKCβ1 isozymes. It is also a potent inhibitor of PKD. Researchers have demonstrated that Gö6976 blocks JNK activation and inhibits PKCα-mediated, TPA-stimulated phosphorylation of CREB at Ser133. Gö6976 is also an effective inhibitor of the tyrosine kinases Jak2 and FLT3, as well as TrkA and TrkB.
References
[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.
