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

European Journal of Medicinal Chemistry

Volumn 70, Issue , 2013, Pages 613-622

  Guan, Ronggui ^a   Xu, Xiaoyu ^a   Chen, Meihui ^a   Hu, Haiyan ^a   Ge, Hu ^a   Wen, Shijun ^b   Zhou, Shiyou ^a   Pi, Rongbiao ^a  

^a SUN YAT SEN UNIVERSITY   (China)

^b SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

Author keywords

Central nervous system; Fasudil; Inhibitors; Rho kinase; RhoA

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; AR 12286; FASUDIL; INDAZOLE DERIVATIVE; ISOQUINOLINE DERIVATIVE; LACTATE DEHYDROGENASE; MESYLIC ACID; MITOGEN ACTIVATED PROTEIN KINASE; MYOSIN LIGHT CHAIN; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHO KINASE INHIBITOR; SR 1459; SR 899; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; BIOLOGICAL ACTIVITY; BRAIN VASOSPASM; CARDIOVASCULAR DISEASE; DIABETES MELLITUS; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; GLOMERULOSCLEROSIS; HIGH THROUGHPUT SCREENING; HUMAN; ISCHEMIC HEART DISEASE; LACTATE DEHYDROGENASE BLOOD LEVEL; NEOPLASM; NEUROLOGIC DISEASE; NONHUMAN; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; REGULATORY MECHANISM; SPONTANEOUSLY HYPERTENSIVE RAT; VASODILATATION;

5-HT; 5-HYDROXYTRYPTAMINE; ACS; ACTIVATOR PROTEIN-1; ACUTE CORONARY SYNDROME; ANGIOTENSIN II TYPE 1 RECEPTOR; AP-1; AT1; C-TERMINAL CYSTEINE-RICH DOMAIN; CENTRAL NERVOUS SYSTEM; CNS; COLLAPSIN RESPONSE MEDIATOR PROTEIN 2; CPI-17; CPK; CRD; CREATINE PHOSPHOKINASE; CRMP-2; DMPK; ENDOTHELIN-1; ERK; ERM; ET-1; EXTRACELLULAR SIGNAL-REGULATED KINASE; EZRIN/RADIXIN/MOESIN FAMILY; FASUDIL; GAPS; GDIS; GDP DISSOCIATION INHIBITORS; GEFS; GTPASE-ACTIVATING PROTEINS; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HCC; HEPATOCELLULAR CARCINOMA; INHIBITORS; INOSITOL 1,4,5-TRISPHOSPHATE; IP3; LACTATE DEHYDROGENASE; LDH; MAXIMAL ELECTROCONVULSIVE SHOCK; MCP-1; MEK; MES; MITOGEN-ACTIVATED PROTEIN KINASE; MLC; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MRCK; MYOSIN LIGHT CHAIN; MYOSIN PHOSPHATASE TARGET SUBUNIT 1; MYOTONIC DYSTROPHY KINASE; MYOTONIC DYSTROPHY KINASE-RELATED CDC42-BINDING KINASE; MYPT-1; NLSS; NUCLEAR LOCALIZATION SIGNALS; OPN; OPTIC NERVE; PAH; PAI-1; PENTYLENETETRAZOLE; PH; PHOSPHATASE AND TENSIN HOMOLOG DELETED ON CHROMOSOME 10; PKC-POTENTIATED INHIBITORY PROTEIN 17; PLASMINOGEN ACTIVATOR INHIBITOR-1; PLECKSTRIN HOMOLOGY; PTEN; PTZ; PULMONARY ARTERIAL HYPERTENSION; RBD; RHO KINASE; RHO-BINDING DOMAIN; RHO-KINASE; RHOA; ROCK; UBIQUITIN-PROTEASOME SYSTEM; UPS; VA; VASCULAR CELL ADHESION MOLECULE-1; VASCULAR SMOOTH MUSCLE CELL; VASOSPASTIC ANGINA; VCAM-1; VSMC;

ANIMALS; DISEASE; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; RHO-ASSOCIATED KINASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84887084044     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2013.10.048     Document Type: Article

References (71)

1. K. Satoh, Y. Fukumoto, and H. Shimokawa Rho-kinase: important new therapeutic target in cardiovascular diseases Am. J. Physiol. Heart Circ. Physiol. 301 2011 H287 H296
2. H.B. Tan, Y.S. Zhong, Y. Cheng, and X. Shen Rho/ROCK pathway and neural regeneration: a potential therapeutic target for central nervous system and optic nerve damage Int. J. Ophthalmol. 4 2011 652 657
3. B.K. Mueller, H. Mack, and N. Teusch Rho kinase, a promising drug target for neurological disorders Nat. Rev. Drug Discov. 4 2005 387 398 (Pubitemid 40704122)
4. M. Liu, F. Bi, X. Zhou, and Y. Zheng Rho GTPase regulation by miRNAs and covalent modifications Trends Cell Biol. 22 2012 365 373
5. R. Shahin, S. Alqtaishat, and M.O. Taha Elaborate ligand-based modeling reveal new submicromolar Rho kinase inhibitors J. Comput. Aided Mol. Des. 26 2012 249 266
6. Q. Zhou, C. Gensch, and J.K. Liao Rho-associated coiled-coil-forming kinases (ROCKs): potential targets for the treatment of atherosclerosis and vascular disease Trends Pharmacol. Sci. 32 2011 167 173
7. H. Yamaguchi, M. Kasa, M. Amano, K. Kaibuchi, and T. Hakoshima Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil Structure 14 2006 589 600 (Pubitemid 43363491)
8. M. Jacobs, K. Hayakawa, L. Swenson, S. Bellon, M. Fleming, P. Taslimi, and J. Doran The structure of dimeric ROCK I reveals the mechanism for ligand selectivity J. Biol. Chem. 281 2006 260 268 (Pubitemid 43671185)
9. R. Garg, K. Riento, N. Keep, J.D. Morris, and A.J. Ridley N-terminus-mediated dimerization of ROCK-I is required for RhoE binding and actin reorganization Biochem. J. 411 2008 407 414 (Pubitemid 351580193)
10. R. Dvorsky, L. Blumenstein, I.R. Vetter, and M.R. Ahmadian Structural insights into the interaction of ROCKI with the switch regions of RhoA J. Biol. Chem. 279 2004 7098 7104 (Pubitemid 38248856)
11. A.L. Couzens, V. Saridakis, and M.P. Scheid The hydrophobic motif of ROCK2 requires association with the N-terminal extension for kinase activity Biochem. J. 419 2009 141 148
12. K.S. Oh, J. Mun, J.E. Cho, S. Lee, K.Y. Yi, C.J. Lim, J.S. Lee, W.J. Park, and B.H. Lee Discovery of novel scaffolds for Rho kinase 2 inhibitor through TRFRET-based high throughput screening assay Comb. Chem. High Throughput Screen. 16 2013 37 46
13. M. Dong, J.K. Liao, B. Yan, R. Li, M. Zhang, and C.M. Yu A combination of increased Rho kinase activity and N-terminal pro-B-type natriuretic peptide predicts worse cardiovascular outcome in patients with acute coronary syndrome Int. J. Cardiol. 167 2013 2813 2819
14. M. Dong, B.P. Yan, J.K. Liao, Y.Y. Lam, G.W. Yip, and C.M. Yu Rho-kinase inhibition: a novel therapeutic target for the treatment of cardiovascular diseases Drug Discov. Today 15 2010 622 629
15. Q. Li, Y. Chen, L. Sun, G. Fu, and L. Guo Vasodilatation produced by fasudil mesylate in vivo and in vitro Vascul. Pharmacol. 55 2011 121 126
16. S.Y. Yoo, J. Kim, S. Cheong, D.H. Shin, J. Jang, C. Lee, S.J. Tahk, J.H. Shin, S.Y. Choi, and M.H. Yoon Rho-associated kinase 2 polymorphism in patients with vasospastic angina Korean Circ. J. 42 2012 406 413
17. H. Fujita, Y. Fukumoto, K. Saji, K. Sugimura, J. Demachi, J. Nawata, and H. Shimokawa Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension Heart Vessels 25 2010 144 149
18. V. Gupta, N. Gupta, I.H. Shaik, R. Mehvar, I.F. McMurtry, M. Oka, E. Nozik-Grayck, M. Komatsu, and F. Ahsan Liposomal fasudil, a rho-kinase inhibitor, for prolonged pulmonary preferential vasodilation in pulmonary arterial hypertension J. Controlled Release 167 2013 189 199
19. D. Gonzalez-Forero, F. Montero, V. Garcia-Morales, G. Dominguez, L. Gomez-Perez, J.M. Garcia-Verdugo, and B. Moreno-Lopez Endogenous Rho-kinase signaling maintains synaptic strength by stabilizing the size of the readily releasable pool of synaptic vesicles J. Neurosci. 32 2012 68 84
20. Y. Hou, L. Zhou, Q.D. Yang, X.P. Du, M. Li, M. Yuan, and Z.W. Zhou Changes in hippocampal synapses and learning-memory abilities in a streptozotocin-treated rat model and intervention by using fasudil hydrochloride Neuroscience 200 2012 120 129
21. M. Raad, T. El Tal, R. Gul, S. Mondello, Z. Zhang, R.M. Boustany, J. Guingab, K.K. Wang, and F. Kobeissy Neuroproteomics approach and neurosystems biology analysis: ROCK inhibitors as promising therapeutic targets in neurodegeneration and neurotrauma Electrophoresis 33 2012 3659 3668
22. B. Villar-Cheda, A. Dominguez-Meijide, B. Joglar, A.I. Rodriguez-Perez, M.J. Guerra, and J.L. Labandeira-Garcia Involvement of microglial RhoA/Rho-kinase pathway activation in the dopaminergic neuron death. Role of angiotensin via angiotensin type 1 receptors Neurobiol. Dis. 47 2012 268 279
23. L. Tonges, T. Frank, L. Tatenhorst, K.A. Saal, J.C. Koch, E.M. Szego, M. Bahr, J.H. Weishaupt, and P. Lingor Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson's disease Brain 135 2012 3355 3370
24. A. Koumura, J. Hamanaka, K. Kawasaki, K. Tsuruma, M. Shimazawa, I. Hozumi, T. Inuzuka, and H. Hara Fasudil and ozagrel in combination show neuroprotective effects on cerebral infarction after murine middle cerebral artery occlusion J. Pharmacol. Exp. Ther. 338 2011 337 344
25. S. Inan, and K. Buyukafsar Antiepileptic effects of two Rho-kinase inhibitors, Y-27632 and fasudil, in mice Br. J. Pharmacol. 155 2008 44 51
26. E. Yoshimi, H. Yamamoto, Y. Furuichi, Y. Shimizu, and N. Takeshita Sustained analgesic effect of the Rho kinase inhibitor AS1892802 in rat models of chronic pain J. Pharmacol. Sci. 114 2010 119 122
27. A.A. Pineda, M. Minohara, N. Kawamura, T. Matsushita, R. Yamasaki, X. Sun, H. Piao, H. Shimokawa, and J. Kira Preventive and therapeutic effects of the selective Rho-kinase inhibitor fasudil on experimental autoimmune neuritis J. Neurol. Sci. 306 2011 115 120
28. M. Chen, A. Liu, Y. Ouyang, Y. Huang, X. Chao, and R. Pi Fasudil and its analogs: a new powerful weapon in the long war against central nervous system disorders? Expert Opin. Invest. Drugs 22 2013 537 550
29. N. Rath, and M.F. Olson Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy EMBO Rep. 13 2012 900 908
30. H. Nakabayashi, and K. Shimizu HA1077, a Rho kinase inhibitor, suppresses glioma-induced angiogenesis by targeting the Rho-ROCK and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signal pathways Cancer Sci. 102 2011 393 399
31. X. Yang, J. Di, Y. Zhang, S. Zhang, J. Lu, J. Liu, and W. Shi The Rho-kinase inhibitor inhibits proliferation and metastasis of small cell lung cancer Biomed. Pharmacother. 66 2012 221 227
32. H. Eldawoody, H. Shimizu, N. Kimura, A. Saito, T. Nakayama, A. Takahashi, and T. Tominaga Fasudil, a Rho-kinase inhibitor, attenuates induction and progression of cerebral aneurysms: experimental study in rats using vascular corrosion casts Neurosci. Lett. 470 2010 76 80
33. Y. Takeba, N. Matsumoto, M. Watanabe, S. Takenoshita-Nakaya, Y. Ohta, T. Kumai, M. Takagi, S. Koizumi, T. Asakura, and T. Otsubo The Rho kinase inhibitor fasudil is involved in p53-mediated apoptosis in human hepatocellular carcinoma cells Cancer Chemother. Pharmacol. 69 2012 1545 1555
34. H. Li, W. Peng, W. Jian, Y. Li, Q. Li, W. Li, and Y. Xu ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion Cardiovasc. Diabetol. 11 2012 65
35. G. Mangialardi, R. Katare, A. Oikawa, M. Meloni, C. Reni, C. Emanueli, and P. Madeddu Diabetes causes bone marrow endothelial barrier dysfunction by activation of the RhoA-Rho-associated kinase signaling pathway Arterioscler. Thromb. Vasc. Biol. 33 2013 555 564
36. F. Peng, D. Wu, B. Gao, A.J. Ingram, B. Zhang, K. Chorneyko, R. McKenzie, and J.C. Krepinsky RhoA/Rho-kinase contribute to the pathogenesis of diabetic renal disease Diabetes 57 2008 1683 1692
37. J.W. Park, C.H. Park, I.J. Kim, E.H. Bae, S.K. Ma, J.U. Lee, and S.W. Kim Rho kinase inhibition by fasudil attenuates cyclosporine-induced kidney injury J. Pharmacol. Exp. Ther. 338 2011 271 279
38. N. Wang, P. Guan, J.P. Zhang, Y.Z. Chang, L.J. Gu, F.K. Hao, Z.H. Shi, F.Y. Wang, and L. Chu Preventive effects of fasudil on adriamycin-induced cardiomyopathy: possible involvement of inhibition of RhoA/ROCK pathway Food Chem. Toxicol. 49 2011 2975 2982
39. R.D. Williams, G.D. Novack, T. van Haarlem, C. Kopczynski, and A.R.P.A.S. Group Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension Am. J. Ophthalmol. 152 2011 834 841
40. H. Huang, D. Kong, K.H. Byun, C. Ye, S. Koda, D.H. Lee, B.C. Oh, S.W. Lee, B. Lee, J.M. Zabolotny, M.S. Kim, C. Bjorbaek, B.B. Lowell, and Y.B. Kim Rho-kinase regulates energy balance by targeting hypothalamic leptin receptor signaling Nat. Neurosci. 15 2012 1391 1398
41. W.G. Duan, S.T. Yuan, H. Liao, M. Yan, and L.Y. Zhang Advances in the study of Rho kinase and its inhibitors Yao Xue Xue Bao 42 2007 1013 1022
42. M. Tamura, H. Nakao, H. Yoshizaki, M. Shiratsuchi, H. Shigyo, H. Yamada, T. Ozawa, J. Totsuka, and H. Hidaka Development of specific Rho-kinase inhibitors and their clinical application Biochim. Biophys. Acta 1754 2005 245 252 (Pubitemid 41797705)
43. M. Iwakubo, A. Takami, Y. Okada, T. Kawata, Y. Tagami, M. Sato, T. Sugiyama, K. Fukushima, S. Taya, M. Amano, K. Kaibuchi, and H. Iijima Design and synthesis of rho kinase inhibitors (III) Bioorg. Med. Chem. 15 2007 1022 1033 (Pubitemid 44880705)
44. P. Ray, J. Wright, J. Adam, J. Bennett, S. Boucharens, D. Black, A. Cook, A.R. Brown, O. Epemolu, D. Fletcher, A. Haunso, M. Huggett, P. Jones, S. Laats, A. Lyons, J. Mestres, J. de Man, R. Morphy, Z. Rankovic, B. Sherborne, L. Sherry, N. van Straten, P. Westwood, and G.Z. Zaman Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors Bioorg. Med. Chem. Lett. 21 2011 97 101
45. D. Lavogina, K. Kalind, J. Bredihhina, M. Hurt, A. Vaasa, M. Kasari, E. Enkvist, G. Raidaru, and A. Uri Conjugates of 5-isoquinolinesulfonylamides and oligo-D-arginine possess high affinity and selectivity towards Rho kinase (ROCK) Bioorg. Med. Chem. Lett. 22 2012 3425 3430
46. K.K. Ho, J.R. Beasley, L. Belanger, D. Black, J.H. Chan, D. Dunn, B. Hu, A. Klon, S.G. Kultgen, M. Ohlmeyer, S.M. Parlato, P.C. Ray, Q. Pham, Y. Rong, A.L. Roughton, T.L. Walker, J. Wright, K. Xu, Y. Xu, L. Zhang, and M. Webb Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model Bioorg. Med. Chem. Lett. 19 2009 6027 6031
47. A.J. Henderson, M. Hadden, C. Guo, N. Douglas, H. Decornez, M.R. Hellberg, A. Rusinko, M. McLaughlin, N. Sharif, C. Drace, and R. Patil 2,3-Diaminopyrazines as Rho kinase inhibitors Bioorg. Med. Chem. Lett. 20 2010 1137 1140
48. R. Li, M.P. Martin, Y. Liu, B. Wang, R.A. Patel, J.Y. Zhu, N. Sun, R. Pireddu, N.J. Lawrence, J. Li, E.B. Haura, S.S. Sung, W.C. Guida, E. Schonbrunn, and S.M. Sebti Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors J. Med. Chem. 55 2012 2474 2478
49. Y. Feng, M.D. Cameron, B. Frackowiak, E. Griffin, L. Lin, C. Ruiz, T. Schröter, and P. LoGrasso Structure-activity relationships, and drug metabolism and pharmacokinetic properties for indazole piperazine and indazole piperidine inhibitors of ROCK-II Bioorg. Med. Chem. Lett. 17 2007 2355 2360 (Pubitemid 46484293)
50. H. Cui, Krista B. Goodman, Sarah E. Dowdell, Dimitri E. Gaitanopoulos, Robert L. Ivy, Clark A. Sehon, Robert A. Stavenger, Gren Z. Wang, and Andrew Q. Viet Development of dihydropyridone indazole amides as selective rho-kinase inhibitors J. Med. Chem. 50 2007 6 9 (Pubitemid 46105495)
51. C.A. Sehon, G.Z. Wang, A.Q. Viet, K.B. Goodman, S.E. Dowdell, P.A. Elkins, S.F. Semus, C. Evans, L.J. Jolivette, R.B. Kirkpatrick, E. Dul, S.S. Khandekar, T. Yi, L.L. Wright, G.K. Smith, D.J. Behm, R. Bentley, C.P. Doe, E. Hu, and D. Lee Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases J. Med. Chem. 51 2008 6631 6634
52. Y.T. Chen, T.D. Bannister, A. Weiser, E. Griffin, L. Lin, C. Ruiz, M.D. Cameron, S. Schurer, D. Duckett, T. Schroter, P. LoGrasso, and Y. Feng Chroman-3-amides as potent Rho kinase inhibitors Bioorg. Med. Chem. Lett. 18 2008 6406 6409
53. Y. Yin, L. Lin, C. Ruiz, M.D. Cameron, J. Pocas, W. Grant, T. Schroter, W. Chen, D. Duckett, S. Schurer, P. Lograsso, and Y. Feng Benzothiazoles as Rho-associated kinase (ROCK-II) inhibitors Bioorg. Med. Chem. Lett. 19 2009 6686 6690
54. X. Fang, Y. Yin, Y.T. Chen, L. Yao, B. Wang, M.D. Cameron, L. Lin, S. Khan, C. Ruiz, T. Schroter, W. Grant, A. Weiser, J. Pocas, A. Pachori, S. Schurer, P. Lograsso, and Y. Feng Tetrahydroisoquinoline derivatives as highly selective and potent Rho kinase inhibitors J. Med. Chem. 53 2010 5727 5737
55. S. Chowdhury, E.H. Sessions, J.R. Pocas, W. Grant, T. Schroter, L. Lin, C. Ruiz, M.D. Cameron, S. Schurer, P. LoGrasso, T.D. Bannister, and Y. Feng Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I) Bioorg. Med. Chem. Lett. 21 2011 7107 7112
56. X. Fang, Y.T. Chen, E.H. Sessions, S. Chowdhury, T. Vojkovsky, Y. Yin, J.R. Pocas, W. Grant, T. Schroter, L. Lin, C. Ruiz, M.D. Cameron, P. LoGrasso, T.D. Bannister, and Y. Feng Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors Bioorg. Med. Chem. Lett. 21 2011 1844 1848
57. E.H. Sessions, S. Chowdhury, Y. Yin, J.R. Pocas, W. Grant, T. Schroter, L. Lin, C. Ruiz, M.D. Cameron, P. LoGrasso, T.D. Bannister, and Y. Feng Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-II) Bioorg. Med. Chem. Lett. 21 2011 7113 7118
58. Y. Yin, M.D. Cameron, L. Lin, S. Khan, T. Schroter, W. Grant, J. Pocas, Y.T. Chen, S. Schurer, A. Pachori, P. LoGrasso, and Y.B. Feng Discovery of potent and selective urea-based ROCK inhibitors and their effects on intraocular pressure in rats ACS Med. Chem. Lett. 1 2010 175 179
59. Y. Yin, L. Lin, C. Ruiz, S. Khan, M.D. Cameron, W. Grant, J. Pocas, N. Eid, H. Park, T. Schroter, P.V. Lograsso, and Y. Feng Synthesis and biological evaluation of urea derivatives as highly potent and selective rho kinase inhibitors J. Med. Chem. 56 2013 3568 3581
60. R.A. Stavenger, H. Cui, S.E. Dowdell, R.G. Franz, D.E. Gaitanopoulos, K.B. Goodman, M.A. Hilfiker, R.L. Ivy, J.D. Leber, J.P. Marino Jr., H.J. Oh, A.Q. Viet, W. Xu, G. Ye, D. Zhang, Y. Zhao, L.J. Jolivette, M.S. Head, S.F. Semus, P.A. Elkins, R.B. Kirkpatrick, E. Dul, S.S. Khandekar, T. Yi, D.K. Jung, L.L. Wright, G.K. Smith, D.J. Behm, C.P. Doe, R. Bentley, Z.X. Chen, E. Hu, and D. Lee Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity J. Med. Chem. 50 2007 2 5 (Pubitemid 46105494)
61. T. Bosanac, E.R. Hickey, J. Ginn, M. Kashem, S. Kerr, S. Kugler, X. Li, A. Olague, S. Schlyer, and E.R. Young Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 3, aryl substituted pyrrolidines Bioorg. Med. Chem. Lett. 20 2010 3746 3749
62. E.M. Storck, and B. Wojciak-Stothard Rho GTPases in pulmonary vascular dysfunction Vascul. Pharmacol. 58 2013 202 210
63. M. Musilli, V. Nicolia, S. Borrelli, S. Scarpa, and G. Diana Behavioral effects of Rho GTPase modulation in a model of Alzheimer's disease Behav. Brain Res. 237C 2012 223 229
64. S.K. Goswami, M.K. Pandre, R. Jamwal, S. Dethe, A. Agarwal, and M.N. Inamdar Screening for Rho-kinase 2 inhibitory potential of Indian medicinal plants used in management of erectile dysfunction J. Ethnopharmacol. 144 2012 483 489
65. M. Shen, H. Yu, Y. Li, P. Li, P. Pan, S. Zhou, L. Zhang, S. Li, S.M. Lee, and T. Hou Discovery of Rho-kinase inhibitors by docking-based virtual screening Mol. Biosyst. 9 2013 1511 1521
66. M. Shen, S. Zhou, Y. Li, P. Pan, L. Zhang, and T. Hou Discovery and optimization of triazine derivatives as ROCK1 inhibitors: molecular docking, molecular dynamics simulations and free energy calculations Mol. Biosyst. 9 2013 361 374
67. H. Yamaguchi, Y. Miwa, M. Kasa, K. Kitano, M. Amano, K. Kaibuchi, and T. Hakoshima Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y-27632 J. Biochem. 140 2006 305 311 (Pubitemid 44703147)
68. J.D. Ginn, T. Bosanac, R. Chen, C. Cywin, E. Hickey, M. Kashem, S. Kerr, S. Kugler, X. Li, A. Prokopowicz 3rd, S. Schlyer, J.D. Smith, M.R. Turner, F. Wu, and E.R. Young Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 2, optimization for blood pressure reduction in spontaneously hypertensive rats Bioorg. Med. Chem. Lett. 20 2010 5153 5156
69. R.A. Patel, K.D. Forinash, R. Pireddu, Y. Sun, N. Sun, M.P. Martin, E. Schonbrunn, N.J. Lawrence, and S.M. Sebti RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer Cancer Res. 72 2012 5025 5034
70. R. Pireddu, K.D. Forinash, N.N. Sun, M.P. Martin, S.S. Sung, B. Alexander, J.Y. Zhu, W.C. Guida, E. Schonbrunn, S.M. Sebti, and N.J. Lawrence Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2) MedChemComm 3 2012 699 709
71. J.D. Doran, X. Liu, P. Taslimi, A. Saadat, and T. Fox New insights into the structure-function relationships of Rho-associated kinase: a thermodynamic and hydrodynamic study of the dimer-to-monomer transition and its kinetic implications Biochem. J. 384 2004 255 262 (Pubitemid 39656237)