Applications for ROCK kinase inhibiton

被引：301

作者：

Olson, Michael F. ^{[1
]}

机构：

[1] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland

来源：

CURRENT OPINION IN CELL BIOLOGY | 2008年 / 20卷 / 02期

关键词：

D O I：

10.1016/j.ceb.2008.01.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

ROCK kinases, which play central roles in the organization of the actin cytoskeleton, are tantalizing targets for the treatment of human diseases. Deletion of ROCK I in mice revealed a role in the pathophysiological responses to high blood pressure, and validated ROCK inhibition for the treatment of specific types of cardiovascular disease. To date, the only ROCK inhibitor employed clinically in humans is fasudil, which has been used safely in Japan since 1995 for the treatment of cerebral vasospasm. Clinical trials, mostly focusing on the cardiovascular system, have uncovered beneficial effects of fasudil for additional indications. Intriguing recent findings also suggest significant potential for ROCK inhibitors in the production and implantation of stem cells for disease therapies.

引用

页码：242 / 248

页数：7

共 54 条

[1] The selectivity of protein kinase inhibitors: a further update [J].

Bain, Jenny ;

Plater, Lorna ;

Elliott, Matt ;

Shpiro, Natalia ;

Hastie, C. James ;

Mclauchlan, Hilary ;

Klevernic, Iva ;

Arthur, J. Simon C. ;

Alessi, Dario R. ;

Cohen, Philip .

BIOCHEMICAL JOURNAL, 2007, 408 :297-315

[2] Resensitization of breast cancer cells to anoikis by Tropomyosin-1: role of Rho kinase-dependent cytoskeleton and adhesion [J].

Bharadwaj, S ;

Thanawala, R ;

Bon, G ;

Falcioni, R ;

Prasad, GL .

ONCOGENE, 2005, 24 (56) :8291-8303

[3] Models of the cooperative mechanism for Rho effector recognition - Implications for RhoA-mediated effector activation [J].

Blumenstein, L ;

Ahmadian, MR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (51) :53419-53426

[4] Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis [J].

Chang, Jiang ;

Xie, Min ;

Shah, Viraj R. ;

Schneider, Michael D. ;

Entman, Mark L. ;

Wei, Lei ;

Schwartz, Robert J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (39) :14495-14500

[5] Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I [J].

Coleman, ML ;

Sahai, EA ;

Yeo, M ;

Bosch, M ;

Dewar, A ;

Olson, MF .

NATURE CELL BIOLOGY, 2001, 3 (04) :339-345

[6] Rho GTPase signalling pathways in the morphological changes associated with apoptosis [J].

Coleman, ML ;

Olson, MF .

CELL DEATH AND DIFFERENTIATION, 2002, 9 (05) :493-504

[7] Conditional regulation of a ROCK-estrogen receptor fusion protein [J].

Croft, DR ;

Olson, MF .

METHODS IN ENZYMOLOGY, VOL 406, REGULATORS AND EFFECTORS OF SMALL GTPASES: RHO FAMILY, 2006, 406 :541-553

[8] Signaling mechanism of renal fibrosis in unilateral ureteral obstructive kidney disease in ROCK1 knockout mice [J].

Fu, Ping ;

Liu, Fang ;

Su, Spencer ;

Wang, Wansheng ;

Huang, Xiao R. ;

Entman, Mark L. ;

Schwartz, Robert J. ;

Wei, Lei ;

Lan, Hui Y. .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (11) :3105-3114

[9] Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension [J].

Fukumoto, Y ;

Matoba, T ;

Ito, A ;

Tanaka, H ;

Kishi, T ;

Hayashidani, S ;

Abe, K ;

Takeshita, A ;

Shimokawa, H .

HEART, 2005, 91 (03) :391-392

[10] Anti-ischemic effects of fasudil, a specific Rho-kinase inhibitor, in patients with stable effort angina [J].

Fukumoto, Yoshihiro ;

Mohri, Masahiro ;

Inokuchi, Kosuke ;

Ito, Akira ;

Hirakawa, Yoji ;

Masumoto, Akihiro ;

Hirooka, Yoshitaka ;

Takeshita, Akira ;

Shimokawa, Hiroaki .

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2007, 49 (03) :117-121

← 1 2 3 4 5 6 →