化学性质

资料参考

Ro 31-8220是蛋白激酶C的选择性抑制剂,对PKC-α\PKC-βI\PKC-βII\PKC-γ和PKC-ε的IC50值分别为5 nM\24 nM\14 nM\27 nM和24 nM[1].

PKC是一种单体Ca2+和磷脂依赖性丝氨酸/苏氨酸蛋白激酶,在生长因子激活的信号通路与恶变中起着重要作用.

Ro 31-8220是一种选择性的PKC抑制剂.CRo 31-8220上调生长因子诱导的c-Jun表达,但抑制MKP-1与c-Fos表达.RO-31-8220强效刺激应激活化蛋白激酶JNK1,但此作用与PKC无关[2].在外周血单核细胞中,Ro 31-8220抑制分裂素诱导的白介素(IL)-2生成以及IL-2依赖性T淋巴细胞增殖,相应IC50值为80 nM和350 nM.此外,Ro 31-8220(400 nM)也抑制了27%的IL-2Rα(CD25)表达,这表明Ro 31-8220可以抑制早期与晚期T细胞活化[3].

在大鼠脂肪细胞和L6肌管细胞中,RO31-8220激活c-Jun N-末端激酶(JNK)和糖原合成酶(GS),促进葡萄糖合成糖原.此外,RO31-8220抑制细胞外信号调节激酶1/2(ERK1/2)活性,此作用与PKC无关[4].

参考文献：
[1].  Wilkinson SE, Parker PJ, Nixon JS. Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. Biochem J, 1993, 294 ( Pt 2): 335-337.
[2].  Beltman J, McCormick F, Cook SJ. The selective protein kinase C inhibitor, Ro-31-8220, inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, induces c-Jun expression, and activates Jun N-terminal kinase. J Biol Chem, 1996, 271(43): 27018-27024.
[3].  Geiselhart L, Conti DJ, Freed BM. RO 31-8220, a novel protein kinase C inhibitor, inhibits early and late T cell activation events. Transplantation, 1996, 61(11): 1637-1642.
[4].  Standaert ML, Bandyopadhyay G, Antwi EK, et al. RO 31-8220 activates c-Jun N-terminal kinase and glycogen synthase in rat adipocytes and L6 myotubes. Comparison to actions of insulin.

生物活性