Go6983 is a pan-PKC inhibitor against for PKCα, PKCβ, PKCγ and PKCδ with IC50 of 7 nM, 7 nM, 6 nM and 10 nM, respectively and less potent to PKCζ and inactive to PKCμ.
Protein kinase C (PKC) is a serine/threonine protein kinase, which plays a crucial role in signaling transduction mechanisms in many cell types and tissues. Gö 6983 is a pan-PKC inhibitor with IC50 values of 7nM, 7nM, 6nM, 10nM and 60nM (measure by protein kinase assay) for PKCα, PKCβ, PKCγ, PKCδ and PKCζ, whereas no activity against PKCμ with IC50 value of 20000nM. Gö 6983 is different with the normal pan-PKC inhibitor, such as staurosporine (IC50=40nM), for it has no effect on PKCμ, facilitating its ability to selective determination of PKCμ kinase activity in the presence of other PKC isoenzymes[1]. Treatment with Gö6983 induced the surface expression of NCRs, including NCR1, NCR2 and NCR3 (measured by relative MFI ratio) in a time- and dose-dependent manner, in primary NK cells. Pre-treatment with Gö6983 for 4h enhanced NK cell-mediated tumor cell killing at an E:T ratio of 3:1, performing as increased apoptosis and cytotoxicity on HepG2, Hep3B and HeLa cells, but has no cytotoxicity itself. Injection with 22.0ug of Gö6983 once daily on days-2, 0, 2, and 4 strongly inhibited tumor metastasis in pulmonary tumor metastasis models[2]. Inhibition of PKC through Gö 6983 could maintain ESC-specific epigenetic modifications at the chromatin domains of pluripotency genes and, thus maintain the expression of these genes in rat embryonic stem cells[3]. It was found that Gö6983 could also inhibit the activity of PfPKB, a protein kinase B homologue in Plasmodium falciparum[4].
作用机制
Gö 6983 acts at the ATP binding site which is highly conserved across PKC isoforms. [5]
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