Y-33075 is a potent ROCK (Rho-associated protein kinase) inhibitor with an IC50 value of 3.6nM[1]. ROCK is a serine-threonine kinase belonging to the AGC (PKA/PKG/PKC) family of kinases and is present in mammals, zebrafish, Xenopus laevis, invertebrates, and chickens[2]. Y-33075 exhibits neuroprotective effects on retinal ganglion cells (RGCs)[3]. Treatment of Xenopus laevis with Y-33075 can disrupt the homeostasis of ciliated epithelial tissues, leading to abnormal epithelial growth at the tail margins[4].
In vitro, treatment of primary hepatic stellate cells (HSCs) isolated from FVB/NJ mice and the immortalized human hepatic stellate cell line (TWNT-4 cells) with Y-33075 (10nM-10µM) for 24h significantly reduced the contraction, fibrosis, and proliferation of activated mouse HSCs and TWNT-4 cells, while significantly increasing the migration of mouse HSCs[5]. Treatment of activated LX-2 cells with Y-33075 (10nM) downregulated the expression of ROCK and p-MLC and upregulated the expression of cAMP and PKA[6].
References:
[1] Vercammen H, Ondra M, Kotulova J, et al. “Keep on ROCKIn”: Repurposed ROCK inhibitors to boost corneal endothelial regeneration[J]. Biomedicine & Pharmacotherapy, 2024, 174: 116435.
[2] Amin F, Ahmed A, Feroz A, et al. An update on the association of protein kinases with cardiovascular diseases[J]. Current Pharmaceutical Design, 2019, 25(2): 174-183.
[3] Reboussin É, Bastelica P, Benmessabih I, et al. Evaluation of Rho kinase inhibitor effects on neuroprotection and neuroinflammation in an ex-vivo retinal explant model[J]. Acta Neuropathologica Communications, 2024, 12(1): 150.
[4] Khan F, Pitstick L, Lara J, et al. Rho-Associated protein kinase activity is required for tissue homeostasis in the Xenopus laevis ciliated epithelium[J]. Journal of Developmental Biology, 2024, 12(2): 17.
[5] Bachtler N, Torres S, Ortiz C, et al. The non-selective Rho-kinase inhibitors Y-27632 and Y-33075 decrease contraction but increase migration in murine and human hepatic stellate cells[J]. PLoS One, 2023, 18(1): e0270288.
[6] Zeng R, Guo Y, Qi J, et al. Dantao formula alleviates hepatic fibrosis and portal hypertension via modulation of the cAMP/PKA/ROCK signaling pathway in hepatic stellate cells[J]. Journal of Ethnopharmacology, 2025: 120650.
Y-33075是一种有效的ROCK（Rho相关蛋白激酶）抑制剂，IC50值为3.6nM[1]。ROCK是一种属于丝氨酸-苏氨酸激酶AGC（PKA/PKG/PKC）家族的激酶，存在于哺乳动物、斑马鱼、非洲爪蟾、无脊椎动物和鸡中[2]。Y-33075对视网膜神经节细胞（RGCs）具有神经保护作用[3]。Y-33075处理非洲爪蟾，能够破坏纤毛上皮组织稳态，导致尾部边缘出现异常上皮生长[4]。
在体外，Y-33075（10nM-10µM）处理从FVB/NJ小鼠分离的原代肝星状细胞（HSC）和永生化人肝星状细胞系（TWNT-4细胞）24h，显著降低了激活的小鼠HSC和TWNT-4细胞的收缩、纤维化和增殖，显著增加了小鼠HSC的迁移显著增加[5]。Y-33075（10nM）处理激活的LX-2细胞，下调了ROCK和p-MLC的表达，上调了cAMP和PKA的表达[6]。