Rho Kinase (ROCK) Inhibitors and Their Therapeutic Potential
Rho Kinase (ROCK) Inhibitors and Their Therapeutic Potential
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DOI：
10.1021/acs.jmedchem.5b00683
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发表时间：
2016-03-24
影响因子：
7.3
通讯作者：
Li, Rongshi
中科院分区：
文献类型：
--
作者：
Feng, Yangbo;LoGrasso, Philip V.;Li, Rongshi
Rho激酶（ROCK）属于丝氨酸苏氨酸家族，其抑制影响许多下游底物的功能。因此，ROCK抑制剂在多种病理状况中具有潜在的治疗适用性，包括哮喘、癌症、勃起功能障碍、青光眼、胰岛素抵抗、肾衰竭、神经元变性和骨质疏松症。迄今为止，两种ROCK抑制剂已在日本（法舒地尔和利帕舒地尔）和一种在中国（法舒地尔）被批准用于临床。1995年，法舒地尔被批准用于治疗脑血管痉挛，最近，利帕舒地尔在2014年被批准用于治疗青光眼。本文综述了ROCK的生理学和生物学功能、170多种ROCK抑制剂的性质和发展以及它们的治疗潜力、现状和未来考虑。
Rho kinases (ROCKs) belong to the serine threonine family, the inhibition of which affects the function of many downstream substrates. As such, ROCK inhibitors have potential therapeutic applicability in a wide variety of pathological conditions, including asthma, cancer, erectile dysfunction, glaucoma, insulin resistance, kidney failure, neuronal degeneration, and osteoporosis. To date, two ROCK inhibitors have been approved for clinical use in japan (fasudil and ripasudil) and one in China (fasudil). In 1995 fasudil was approved for the treatment of cerebral vasospasm, and more recently, ripasudil was approved for the treatment of glaucoma in 2014. In this Perspective, we present a comprehensive review of the physiological and biological functions for ROCK, the properties and development of over 170 ROCK inhibitors as well as their therapeutic potential, the current status, and future considerations.