EpigeneticsTGF-beta/Smad-

Ro 31-8220(Bisindolylmaleimide IX)??????????????????PKC???????????????PKC-?????PKC-??I???PKC-??II???PKC-?????PKC-?????IC50?????????5 nM???24 nM???14 nM???27 nM???24 nM???

PKC

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生物活性

Description

Ro 31-8220 mesylate (Bisindolylmaleimide IX) is a pan-PKC inhibitor with IC50 of 5 nM, 24 nM, 14 nM, 27 nM, and 24 nM for PKC-??, PKC-??I, PKC-??II, PKC-??, and PKC-??, respectively.IC50 Value: 5, 24, 14, 27, and 24 nM (PKC ??, PKC ??I, PKC ??II, PKC ??, and PKC) [1]Target: pan-PKCRo 31-8220, a staurosporine (sc-3510) analog, is a cell-permeable inhibitor of PKC (protein kinase C) isoforms PKC ??, PKC ??I, PKC ??II, PKC ??, and PKC ?? (IC50 = 5, 24, 14, 27, and 24 nM, respectively). Ro 31-8220 has also been shown to induce apoptosis in various cell lines, independent of its PKC activity, and to inhibit GSK 3 (IC50 = 6.8nM). Ro 31-8220 is an inhibitor of Cdk2, cyclin A, GSK-3??, MSK1, Pim-3, Polycystin-1, PRK2, Rsk-1 and Rsk-2 and an activator of JNK1.Ro 31-8220 antagonized (IC50, 1.0 microM) the effect of the activator of protein kinase C,12-O-tetradecanoylphorbol 13-acetate (TPA), on histamine-stimulated aminopyrine accumulation. Ro 31-8220 (0.1-2.14 microM) inhibited the aminopyrine response to 0.1 mM carbachol (IC50, 0.78 microM; 49% inhibition at 2.14 microM Ro 31-8220) and shifted the dose-response curve for the effect of carbachol concentration of aminopyrine accumulation downwards and to the right. No inhibition of aminopyrine accumulation induced by histamine was found with Ro 31-8220 (0.1-2.14 microM) [1]. U-87 and A172 cells treated with an IC50 of Ro 31-8220 exhibited nucleosomal DNA fragmentation that coincided with an increase in the number of apoptotic cells. This effect was preceded by the rapid nuclear accumulation of wild-type p53 within 2 hr, and an increased level of the pro-apoptotic protein, insulin-like growth factor-1-binding protein-3, (IGFBP3) but not other p53-regulated proteins such as p21WAF1 or Bax [2].

References

[1].McKenna JP, et al. Inhibition by Ro 31-8220 of acid secretory activity induced by carbachol indicates a stimulatory role for protein kinase C in the action of muscarinic agonists on isolated rat parietal cells. Biochem Pharmacol. 1993 Aug 17;46(4):583-8.

[2].Shen L, et al. Induction of apoptosis in glioblastoma cells by inhibition of protein kinase C and its association with the rapid accumulation of p53 and induction of the insulin-like growth factor-1-binding protein-3. Biochem Pharmacol. 1998 May 15;55(10):1711-9.