生物活性

• 靶点

  PKCβ1 IC50:6.2nM

  PKCα IC50:2.3nM

  PKC (rat brain) IC50:7.9nM

• 描述PKC (Protein kinase C) is a ubiquitous phospholipid-dependent protein kinase which plays a crucial role in signaling transduction related to neuronal function, cell growth and differentiation, cell motility, secretion and cellular metabolism and smooth muscle contraction. Gö6976 is a pan inhibitor of Ca²⁺-dependent PKC isozymes, PKCα and PKCβ1, with IC50 values of 2.3nM and 6.2nM, respectively, but has no effect on Ca²⁺-independent PKC isozymes PKCδ, ε and ζ (measured by enzymatic activities of different PKC isozymes). This facilitates its ability to discriminate between Ca²⁺-dependent and -independent isoforms of PKC in vitro. Incubation with Gö6976 1μM for 72h can induce 90% apoptosis in NB4 cells and complete loss of full-length caspase 3. Meanwhile, caspase 8 can be seen in NB4 cells treated with 10μM Gö6976 for 8h. For Gö6976 is a multiple target inhibitor, it also inhibits JAK2/3 tyrosine kinases, PKCμ, as well as mitotic spindle checkpoint. Gö6976 could reduce the JAK2 auto-kinase activity and JAK3 kinase activity at concentration of 1μM in an in vitro kinase assay. Consistent with this, pre-incubation with Gö6976 could reduce IL2-stimulated phosphorylation of STAT5, the JAK3 dependent signaling, in a dose-dependent manner in peripheral blood-derived lymphocytes incubated with 10mg/ml PHA for 72h. It was reported that the enzyme activity of PKCμ is effectively suppressed by Gö6976 but not by Gö 6983. Gö6976 treatment can potently override a spindle checkpoint–mediated mitotic arrest by abrogating the phosphorylation and kinetochore localization of several spindle checkpoint proteins and cause severe mitotic abnormalities and chromosome alignment defects, which are not properly detected by the drug-inactivated spindle checkpoint.
• 作用机制Gö6976 is an ATP-competitive inhibitor.

• 动物研究
  剂量	Monkey: 2 mg/kg(i.v.) Mice (i.p): 2.5 mg/kg
  给药途径	i.v., i.p.