Advances in the studies of roles of Rho/Rho-kinase in diseases and the development of its inhibitors

Eur J Med Chem. 2013;70:613-22. doi: 10.1016/j.ejmech.2013.10.048. Epub 2013 Oct 25.


RhoA/Rho-kinase pathway plays a pivotal role in numerous fundamental cellular functions including contraction, motility, proliferation, differentiation and apoptosis. The pathway is also involved in the development of many diseases such as vasospasm, pulmonary hypertension, cancer and central nervous systems (CNS) disorders. The inhibitors of Rho kinase have been extensively studied since the Rho/Rho-kinase pathway was verified as a target for a number of diseases. Herein, we reviewed the advances in the studies of the roles of Rho/Rho-kinase in diseases and the development of Rho-kinase inhibitors in recent five years.

Keywords: 5-HT; 5-hydroxytryptamine; ACS; AP-1; AT1; C-terminal cysteine-rich domain; CNS; CPI-17; CPK; CRD; CRMP-2; Central nervous system; DMPK; ERK; ERM; ET-1; Fasudil; GAPs; GDIs; GDP dissociation inhibitors; GEFs; GTPase-activating proteins; HCC; IP3; Inhibitors; LDH; MCP-1; MEK; MES; MLC; MRCK; MYPT-1; NLSs; OpN; PAH; PAI-1; PH; PKC-potentiated inhibitory protein 17; PTEN; PTZ; RBD; ROCK; Rho kinase; Rho-binding domain; Rho-kinase; RhoA; UPS; VA; VCAM-1; VSMC; activator protein-1; acute coronary syndrome; angiotensin II type 1 receptor; central nervous system; collapsin response mediator protein 2; creatine phosphokinase; endothelin-1; extracellular signal-regulated kinase; ezrin/radixin/moesin family; guanine nucleotide exchange factors; hepatocellular carcinoma; inositol 1,4,5-trisphosphate; lactate dehydrogenase; maximal electroconvulsive shock; mitogen-activated protein kinase; monocyte chemoattractant protein-1; myosin light chain; myosin phosphatase target subunit 1; myotonic dystrophy kinase; myotonic dystrophy kinase-related CDC42-binding kinase; nuclear localization signals; optic nerve; pentylenetetrazole; phosphatase and tensin homolog deleted on chromosome 10; plasminogen activator inhibitor-1; pleckstrin homology; pulmonary arterial hypertension; ubiquitin–proteasome system; vascular cell adhesion molecule-1; vascular smooth muscle cell; vasospastic angina.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease*
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism


  • Protein Kinase Inhibitors
  • rho-Associated Kinases