Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity

@article{Hahmann2009RhokinaseIA,
  title={Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity},
  author={Christa Hahmann and Thomas Schroeter},
  journal={Cellular and Molecular Life Sciences},
  year={2009},
  volume={67},
  pages={171-177}
}
The emerging critical implications of Rho/Rho-kinase (ROCK) signaling in neurodegenerative diseases, glaucoma, renoprotection, diabetes and cancer have sparked growing interest in the pharmacological potential of ROCK inhibitors beyond their current application in cardiovascular disease. This article discusses the therapeutic benefits of novel ROCK inhibitors in development, and highlights the recent advances in the current understanding of disease-dependent and isoform-specific functions of… 
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This work will review the strategies currently being used to develop inhibitors of Rho GTPases and downstream signaling kinases and discuss candidate entities.
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This review focuses on the current status of understanding the multiple functions of Rho-ROCK signaling pathways and various modes of regulation of R Ho-Rock activity, thereby orchestrating a concerted functional response.
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Rho kinase (ROCK) inhibitors are a novel potential class of glaucoma therapeutics with multiple compounds currently in Phase II and III US Food and Drug Administration trials in the United States, and there are also animal studies indicating that ROCK inhibitors may improve blood flow to the optic nerve, increase ganglion cell survival, and reduce bleb scarring in glauca surgery.
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Emerging evidence suggests that selective targeting ROCK isoform based on the disease pathophysiology may represent a novel therapeutic approach for the disease treatment including cardiovascular diseases.
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Experimental studies indicate that the RhoA/ROCK pathway in myocardium contributes to cardiac remodeling induced by ischemic injury or persistent hypertrophic stress, thereby leading to cardiac decompensation and heart failure.
Rho-Kinase/ROCK: A Key Regulator of the Cytoskeleton and Cell Polarity
TLDR
This review focuses on the structure, function, and modes of activation and action of Rho‐kinase, which is involved in a wide range of diseases such as vasospasm, pulmonary hypertension, nerve injury, and glaucoma.
A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion.
Rho-associated kinase signalling and the cancer microenvironment: novel biological implications and therapeutic opportunities
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This review addresses the various roles the Rho/ROCK pathway plays in angiogenesis, tumour vascular tone and reciprocal feedback from the tumour microenvironment and explores the potential utility of ROCK inhibitors as effective vascular normalising agents.
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