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Y-27632 is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. IC50 value: 140 nM (Ki) Target: ROCK1 in vitro: Y-27632 inhibits ROCK-II while displaying little activity against PKC, cAMP-dependent protein kinase and myosin light-chain kinase (MLCK) with Ki of 26 uM, 25 uM and > 250 uM, respectively, as well as PKA activated by another Rho-family GTPase member, Cdc42. Y-27632 inhibits smooth-muscle contraction induces by various agonists including phenylephrine, histamine, acetylcholine, serotonin, endothelin, and thromboxane with IC50 of 0.3-1 uM, by selectively inhibiting Ca2+ sensitization. Y-27632 suppresses Rho-induced, p160ROCK-mediated formation of stress fibres in cultured cells. In human embryonic stem (hES) cells, Y-27632 treatment at 10 uM markedly diminishes dissociation-induced apoptosis even in serum-free suspension (SFEB) culture, increases cloning efficiency (from 1% to 27%), facilitates subcloning after gene transfer, and enables SFEB-cultured hES cells to survive and differentiate into Bf1+ cortical and basal telencephalic progenitors. in vivo: Oral administration of Y-27632 at 30 mg/kg significantly decreases the blood pressure in a dose-dependent manner in spontaneous hypertensive rats, renal hypertensive rats, as well as deoxycorticosterone acetate (DOCA)-salt hypertensive rats. When Y-27632 is continuously administered at a rate of 0.55 uL per hour by implanted pumps for 11 days tumor cell invasion (MM1 cells expressing Val14-RhoA in rats) is significantly delayed. By inhibiting ROCK, Y-27632 treatment attenuates hypoxia-induced angiogenesis and vascular remodeling in the pulmonary circulation.
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