Y-27632 dihydrochloride

Y-27632 dihydrochloride, as a selective Rho-kinase inhibitor, is a novel bronchodilator.^[1]

In vitro, treatment with 3 and 10 μM Y-27632 remarkably reduced the maximal contractile response. And Y-27632 (10 μM ) markedly increased the EFS-induced outflow of radioactivity from airway cholinergic nerves by 27% and 54% respectively, in murine and guinea-pig tracheal preparations loaded with [(3)H]-choline.^[2] In vitro, Y-27632 at 10 μM abolished stress fibers in Swiss 3T3 cells, but it had no effect in the G(1)-S phase transition of the cell cycle and cytokinesis.^[3] In vitro, treatment with 10 μM Y-27632 and hypoxia further increased the expression of ACAN and COL2A1 in chondrocytic cells.^[4] In vitro, 100 μM Y-27632 significantly promoted cell proliferation and phagocytosis of trabecular meshwork cells.^[6]

In vivo efficacy test it shown that Y-27632 inhalation (1 mM, 2 min) inhibited acetylcholine- or ovalbumin-induced increase in R(L) and had no changes in mean blood pressure, and the effect last for at least 3 h.^[1] In vivo experiment it indicated that injection 5mg/kg Y-27632 intravenously markedly decreased the serum levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and increased IL-10 level in serum of MRL/lpr mice.^[5] In addition, treatment with 2 or 30 mg/kg body weight of Y-27632 orally in SOD1(G93A) mice, Y-27632 improved motor function in male mice at 30 mg/kg, but it had no benefit at 2 mg/kg.^[7]

References:
[1]Iizuka K, et al. Evaluation of Y-27632, a rho-kinase inhibitor, as a bronchodilator in guinea pigs. Eur J Pharmacol. 2000 Oct 13;406(2):273-9.
[2]Fernandes L, et al. A Rho-kinase inhibitor, Y-27632, reduces cholinergic contraction but not neurotransmitter release. Eur J Pharmacol. 2006 Nov 21;550(1-3):155-61.
[3]Ishizaki T, et al. Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol. 2000 May;57(5):976-83.
[4]Piltti J, et al. Rho-kinase inhibitor Y-27632 and hypoxia synergistically enhance chondrocytic phenotype and modify S100 protein profiles in human chondrosarcoma cells. Sci Rep. 2017 Jun 16;7(1):3708.
[5]Wang Y, et al. Y-27632, a Rho-associated protein kinase inhibitor, inhibits systemic lupus erythematosus. Biomed Pharmacother. 2017 Apr;88:359-366.
[6]Chen W, et al. Rho-Associated Protein Kinase Inhibitor Treatment Promotes Proliferation and Phagocytosis in Trabecular Meshwork Cells. Front Pharmacol. 2020 Mar 17;11:302.
[7]Günther R, et al. The rho kinase inhibitor Y-27632 improves motor performance in male SOD1(G93A) mice. Front Neurosci. 2014 Oct 7;8:304.

Y-27632 dihydrochloride 作为一种选择性 Rho 激酶抑制剂，是一种新型支气管扩张剂。^[1]

在体外，用 3 μM 和 10 μM Y-27632 处理可显着降低最大收缩反应。 Y-27632（10 μM）显着增加 EFS 诱导的气道胆碱能神经放射性流出，分别增加 27% 和 54%，在小鼠和豚鼠气管制剂中加载 [(3)H]-胆碱。^[2] 在体外，10 μM 的 Y-27632 消除了 Swiss 3T3 细胞中的应力纤维，但它对细胞周期和胞质分裂的 G(1)-S 相变没有影响。 ^[3] 在体外，10 μM Y-27632 和低氧处理进一步增加软骨细胞中 ACAN 和 COL2A1 的表达。^[4] 在体外，100 μM Y-27632 显着促进小梁网细胞增殖和吞噬作用。^[6]

体内功效测试表明，吸入 Y-27632（1 mM，2 分钟）可抑制乙酰胆碱或卵清蛋白诱导的 R(L) 增加，并且平均血压没有变化，并且效果至少持续3 h.^[1] 体内实验表明，静脉注射5mg/kg Y-27632可显着降低血清白细胞介素6（IL-6）、IL-1β、肿瘤坏死因子- MRL/lpr 小鼠血清中 α (TNF-α) 和 IL-10 水平升高。^[5] 另外，在 SOD1 中口服 2 或 30 mg/kg 体重的 Y-27632 (G93A) 小鼠，Y-27632 在 30 mg/kg 时改善雄性小鼠的运动功能，但在 2 mg/kg 时没有益处。^[7]