Y-27632, Dihydrochloride Salt (Y27, CAS 129830-38-2), >99%

Solubility: Soluble in DMSO at 160 mg/mL, soluble in ethanol at 12 mg/mL with warming, soluble in water at 90 mg/mL, buffers, serum, or other additives may increase or decrease the aqueous solubility. Y-27632 is a novel and specific Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor. Narumiya, S., et al. 'Use and properties of ROCK-specific inhibitor Y-27632.' Methods Enzymol. 325: 273-284 (2000). This research compound is the dihydrochloride salt form of Y-27632. We also plan to offer the free base form, please see Y-27632, Free Base, Cat. No. Y-5399. Y-27632 inhibited ROCK-I (Ki = 0.22 µM) and ROCK-II (Ki = 0.30 µM) by competing with ATP for its binding to the kinase. Ishizaki, T., et al. 'Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases.' Mol. Pharmacol. 57: 976-983 (2000). Y-27632 selectively inhibited Ca2+ sensitization of smooth muscle and blocked its contraction, prevented Rho-induced, p160ROCK-mediated formation of stress fibers in cultured cells, and dramatically lowered hypertension in several hypertensive rat models. Uehata, M., et al. 'Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension.' Nature 389: 990-994 (1997). Y-27632 inhibited cell transformation mediated by RhoA and its guanine-nucleotide exchange factor (GEF). Sahai, E., et al. 'Transformation mediated by RhoA requires activity of ROCK kinases.' Curr. Biol. 9: 136-145 (1999). Y-27632 inhibited both Rho-mediated activation of actomyosin and invasive activity of rat MM1 hepatoma cells. Continuous delivery of Y-27632 largely prevented the dissemination of MM1 cells implanted into the peritoneal cavity of syngeneic rats. Itoh, K., et al. 'An essential part for Rho-associated kinase in the transcellular invasion of tumor cells.' Nat. Med. 5: 221-225 (1999). Y-27632 blocked chemotactic peptide-induced development of cell polarity and locomotion, and inhibited myosin light chain phosphorylation with similar potency (ED50 = 0.5-1.1 µM). Niggli, V. 'Rho-kinase in human neutrophils: a role in signalling for myosin light chain phosphorylation and cell migration.' FEBS Lett. 445: 69-72 (1999). Y-27632 had antinociceptive properties, possibly by inhibition of Rho-kinase. Buyukafsar, K., et al. 'Rho-kinase inhibitor, Y-27632, has an antinociceptive effect in mice.' Eur. J. Pharmacol. 541: 49-52 (2006). Y-27632 blocked the development of ischemia/reperfusion-induced acute renal failure, possibly by inhibiting myeloperoxidase activity in an early phase after reperfusion. Teraishi, K., et al. 'Preventive effect of Y-27632, a selective Rho-kinase inhibitor, on ischemia/reperfusion-induced acute renal failure in rats.' Eur. J. Pharmacol. 505: 205-211 (2004). Y-27632 prevented intrahepatic metastasis of human hepatocellular carcinoma. Takamura, M., et al. 'Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632.' Hepatology 33: 577-581 (2001). Y-27632 inhibited both of lysophosphatidic acid (LPA)- and fibronectin (FN)-induced migration and morphological change of rat ascites hepatoma (MM1) cells. It impaired LPA- and FN-evoked formation of focal adhesions and actin bundles and suppressed LPA- and FN-induced tyrosine phosphorylation of focal adhesion kinase and paxillin in MM1 cells. Imamura, F., et al. 'Y-27632, an inhibitor of rho-associated protein kinase, suppresses tumor cell invasion via regulation of focal adhesion and focal adhesion kinase.' Jpn. J. Cancer Res. 91: 811-816 (2000).