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2024-09-11
Y-27632&Y-27632 2HCl ROCK inhibitor抑制劑
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1. Molecular Introduction

Product NameY-27632                 

CAS No.: 146986-50-7                             

Formula: C14H21N3O         

Molecular Weight247.34 

AppearanceWhite to off-white powder

Purity98+%

Storage: -20°C, protect from light, stored under   nitrogen

Structure

 


 

                                                                                                                                  

 

                                                                 

Product NameY-27632· 2HCl

CAS No.: 129830-38-2

Formula: C14H21N3O.2HCl 

Molecular Weight320.26

AppearanceWhite   to off-white powder  

Purity98+%S

Storage: 4°C, sealed storage, away from moisture

Structure:

 


 

 

 2. Background Introduction

Rho GTPases belong to Ras superfamily, which is reported to involve in cell migration, phagocytosis, contraction and adhesion. ROCK (also known as Rho-associated kinase) is considered to be one of the most important downstream targets of Rho that is widely investigated. Rho/ROCK signal pathway induces cytoskeletal reorganization, cell migration and stress fiber formation, affects endothelial permeability, tissue constriction and growth, involves in diabetic nephropathy, eye disease, cancer, heart disease, nerve injury disease, hypertension, radiation injury and leukemia. As a novel drug research target, Rho/ROCK signal pathway has received more and more attention [1].  

ROCK (Rho associated coiled coil containing protein kinase) is a type of protein kinase associated with Rho GTPase, primarily functioning as a downstream effector of the Rho family. ROCK plays a crucial role in regulating various biological processes within cells, including affecting adhesion between cells and matrix, participating in cell division and proliferation, regulating cell migration and movement, and influencing cell contraction and morphological changes. Upstream in cellular signaling pathways: ROCK is regulated by Rho GTPase, particularly RhoA. Downstream: ROCK participates in the phosphorylation of various signaling molecules.





The ROCK family of Rho-associated serine-threonine protein kinases is known to play an important role in Rho-mediated cell adhesion and smooth muscle contraction. Y-27632 is a potent, ATP-competitive inhibitor of ROCKs including p160ROCK (Ki = 140 nM) and ROCK2 (IC50 = 800 nM). It also inhibits PRK2 with an IC50 value of 600 nM. One-hour treatment with 10 μM Y-27632 blocks apoptosis of dissociated cultured human embryonic stem cells, increasing cloning efficiency by 25% and sustaining survival up to 30 passages.

 

3.Biological Activity:

Y-27632 is a widely used and highly efficient small molecule specific inhibitor of Rho-associated kinases (ROCK), ATP-competitive inhibitor of ROCK-I and ROCK-II, with Ki values of 0.22 μM and 0.30 μM for ROCK1 and ROCK2, respectively.

Y-27632 attenuates Doxorubicin-induced apoptosis of human cardiac stem cells. Y27632 inhibits ET-1-induced increases in natriuretic peptide production, cell size, protein synthesis, and myofibrillar organization. Y-27632 also suppresses dissociation-induced apoptosis of murine prostate stem/progenitor cells. Y-27632 primes human induced pluripotent stem cells (hIPSCs) to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulatione [2][3][4][5][6][7][8].

In vitro kinase assays demonstrate that Y-27632 exhibits a 20-fold greater preference for ROCK when compared to citron kinase and protein kinase N [9]. Research studies show that Y-27632 treatment of cells leads to inhibition of ROCK phosphorylation of myosin phosphatase subunit 1 (MYPT1) at both Thr853 and Thr696, with a much greater inhibition of Thr853 phosphorylation [10,11]. Y-27632 selectively inhibits smooth-muscle contraction by inhibiting Ca2+ sensitization [12]. Additional research indicates that Y-27632 inhibits dissociation-induced apoptosis of cultured human embryonic stem cells over numerous passages and increases cloning efficiency [13].

 

4. Application

Y-27632/Y-27632 2HCl,it is a small molecule specific inhibitor of Rho related serine threonine protein kinase (ROCK) family, which can prevent apoptosis of stem cellsso it has important application value in maintaining cell survival and function in organoid culture and stem cell research, in addition to its use in cancer and other diseases. The research shows that inhibits systemic lupus erythematosus [14] and Promoted Limbal Epithelial Cell Proliferation and Corneal Wound Healing [15].

 

Chemleader Biomedical Co., Ltd.

E-mail: sales@MedChemLeader.com

Web:  http://www.www-f849.com 

 

[1]. Jia-yin Han, et al. Research progress of Rho/ROCK signal pathway. Yao Xue Xue Bao.  2016 Jun;51(6):853-9. PMID: 29878737

[2]. Xue ZW, et al. Rho-associated coiled kinase inhibitor Y-27632 promotes neuronal-like differentiation of adult human adipose tissue-derived stem cells.Chin Med J (Engl). 2012 Sep;125(18):3332-5. 

[3]. Inan S, et al. Antiepileptic effects of two Rho-kinase inhibitors, Y-27632 and fasudil, in mice. Br J Pharmacol. 2008 Sep;155(1):44-51. 

[4]. Tada S, et al. A selective ROCK inhibitor, Y27632, prevents dimethylnitrosamine-induced hepatic fibrosis in rats. J Hepatol. 2001 Apr;34(4):529-36. 

 [5]. Kan L, et al. Rho-Associated Kinase Inhibitor (Y-27632) Attenuates Doxorubicin-Induced Apoptosis of Human Cardiac Stem Cells. PLoS One. 2015;10(12): e0144513. Published 2015 Dec 8. 

[6]. Maldonado M, et al. ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towardsmesendodermal lineage via epithelial-mesenchymal transition-like modulation. Stem Cell Res. 2016 Sep;17(2):222-227. 

[7]. Zhang L, et al. ROCK inhibitor Y-27632 suppresses dissociation-induced apoptosis of murine prostate stem/progenitor cells and increases their cloning efficiency. PLoS One. 2011;6(3):e18271. Published 2011 Mar 28.

[8]. Ishizaki T, et al. Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol. 2000 May;57(5):976-83. 

[9]. Ishizaki, T. et al. Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol. (2000);57, 976-83.

[10]. Garton, A.J. et al. Quantitative high-throughput cell-based assays for inhibitors of ROCK kinases. Methods Enzymol. (2008);439, 491-500.

[11]. Ramachandran, C. et al. Rho-Rho kinase pathway in the actomyosin contraction and cell-matrix adhesion in immortalized human trabecular meshwork cells. Mol Vis. (2011);17, 1877-90.

[12]. Uehata, M. et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. (1997);389, 990-4.

[13]. Watanabe, K. et al. A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol. (2007);25, 681-6.

[14]. Yuan YW, et al. Y-27632, a Rho-associated protein kinase inhibitor, inhibits systemic lupus erythematosus. Biomedicine & Pharmacotherapy; Volume 88, April 2017, Pages 359-366.

[15]. Chi CS, et al. Y-27632, a ROCK Inhibitor, Promoted Limbal Epithelial Cell Proliferation and Corneal Wound Healing. plos.org; Published: December 16, 2015.


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