GSK429286A

GSK429286A是一种选择性ROCK1和ROCK2抑制剂，IC50值分别为14 nM和63 nM [1]。

Rho-激酶(ROCK) 属于AGC家族(蛋白激酶A、蛋白激酶G和蛋白激酶C)的成员，在促进肌动蛋白肌球蛋白介导的收缩力产生中具有重要作用[2]。

GSK429286A是一种有效ROCK抑制剂，与已报道的ROCK抑制剂Y27632活力不同。GST实验表明，10 μM GSK429286A通过抑制ROCK，可增加MYPT在Thr850位点的磷酸化作用[3]。

自发性高血压雄性Sprague-Dawley大鼠模型实验中，口服给药GSK429286A (30 mg/kg)可降低平均动脉压，治疗2小时左右，最大降压可达到50 mmHg[4]。

参考文献：
[1] Nichols, R. J., et al., Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease. Biochem J, 2009. 424(1): p. 47-60.
[2] Shi, J. , et al., Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment. Cell Death Dis, 2013. 4: p. e483.
[3] Davis, D. A., et al., Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line. BMC Cancer, 2006. 6: p. 22.
[4] Goodman, K. B., et al., Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors. J Med Chem, 2007. 50(1): p. 6-9.