Advances in the development of Rho-associated protein kinase (ROCK) inhibitors

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Reprod., 13, 181, 10.1093/molehr/gal113 Doe, 2007, Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities, J. Pharmacol. Exp. Ther., 320, 89, 10.1124/jpet.106.110635 Leung, 1996, The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton, Mol. Cell. Biol., 16, 5313, 10.1128/MCB.16.10.5313 Matsui, 1996, Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho, EMBO J., 15, 2208, 10.1002/j.1460-2075.1996.tb00574.x Mueller, 2005, Rho kinase, a promising drug target for neurological disorders, Nat. Rev. Drug Discov., 4, 387, 10.1038/nrd1719 Nakagawa, 1996, ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice, FEBS Lett., 392, 189, 10.1016/0014-5793(96)00811-3 Sebbagh, 2001, Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing, Nat. Cell Biol., 3, 346, 10.1038/35070019 Riento, 2005, RhoE function is regulated by ROCK I-mediated phosphorylation, EMBO J., 24, 1170, 10.1038/sj.emboj.7600612 Peterson, 1999, Kinase phosphorylation: keeping it all in the family, Curr. Biol., 9, R521, 10.1016/S0960-9822(99)80326-1 Amano, 1999, The COOH terminus of Rho-kinase negatively regulates rho-kinase activity, J. Biol. Chem., 274, 32418, 10.1074/jbc.274.45.32418 Ishizaki, 1996, The small GTP-binding protein Rho binds to and activates a 160kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase, EMBO J., 15, 1885, 10.1002/j.1460-2075.1996.tb00539.x Pierdomenico, 2009, Prognostic value of different indices of blood pressure variability in hypertensive patients, Am. J. Hypertens., 22, 842, 10.1038/ajh.2009.103 Uehata, 1997, Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension, Nature, 389, 990, 10.1038/40187 Fukumoto, 2005, Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension, Heart, 91, 391, 10.1136/hrt.2003.029470 Löhn, 2009, Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor, Hypertension, 54, 676, 10.1161/HYPERTENSIONAHA.109.134353 Kolavennu, 2008, Targeting of RhoA/ROCK signaling ameliorates progression of diabetic nephropathy independent of glucose control, Diabetes, 57, 714, 10.2337/db07-1241 Vignozzi, 2007, Testosterone regulates RhoA/Rho-kinase signaling in two distinct animal models of chemical diabetes, J. Sex. Med., 4, 620, 10.1111/j.1743-6109.2007.00440.x Kikuchi, 2007, A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats, J. Endocrinol., 192, 595, 10.1677/JOE-06-0045 Kandabashi, 2000, Inhibition of myosin phosphatase by upregulated Rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1, Circulation, 101, 1319, 10.1161/01.CIR.101.11.1319 Shimokawa, 2001, Long-term inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo, Cardiovasc. Res., 51, 169, 10.1016/S0008-6363(01)00291-7 Hattori, 2004, Long-term inhibition of Rho-kinase suppresses left ventricular remodeling after myocardial infarction in mice, Circulation, 109, 2234, 10.1161/01.CIR.0000127939.16111.58 Kishi, 2005, Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure, Circulation, 111, 2741, 10.1161/CIRCULATIONAHA.104.510248 Heijl, 2002, Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial, Arch. Ophthalmol., 120, 1268, 10.1001/archopht.120.10.1268 Sommer, 1991, Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans: the Baltimore Eye Survey, Arch. Ophthalmol., 109, 1090, 10.1001/archopht.1991.01080080050026 Asrani, 2000, Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma, J. Glaucoma, 9, 134, 10.1097/00061198-200004000-00002 Honjo, 2001, Effects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes, Arch. Ophthalmol., 119, 1171, 10.1001/archopht.119.8.1171 Brabeck, 2004, Lesional expression of RhoA and RhoB following traumatic brain injury in humans, J. Neurotrauma, 21, 697, 10.1089/0897715041269597 Aimone, 2004, Spatial and temporal gene expression profiling of the contused rat spinal cord, Exp. Neurol., 189, 204, 10.1016/j.expneurol.2004.05.042 Madura, 2004, Activation of Rho in the injured axons following spinal cord injury, EMBO Rep., 5, 412, 10.1038/sj.embor.7400117 Dubreuil, 2003, Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system, J. Cell Biol., 162, 233, 10.1083/jcb.200301080 Dergham, 2002, Rho signaling pathway targeted to promote spinal cord repair, J. Neurosci., 22, 6570, 10.1523/JNEUROSCI.22-15-06570.2002 Hara, 2000, Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats, J. Neurosurg., 93, 94 Zhou, 2003, Nonsteroidal anti-inflammatory drugs can lower amyloidogenic A{beta}42 by inhibiting Rho, Science, 302, 1215, 10.1126/science.1090154 Pedrini, 2005, Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK, PLoS Med., 2, e18, 10.1371/journal.pmed.0020018 Huentelman, 2009, Peripheral delivery of a ROCK inhibitor improves learning and working memory, Behav. Neurosci., 123, 218, 10.1037/a0014260 Song, 2013, Rho kinase inhibitor fasudil protects against β amyloid induced hippocampal neurodegeneration in rats, CNS Neurosci. Ther., 19, 603, 10.1111/cns.12116 Rikitake, 2005, Inhibition of Rho kinase (ROCK) leads to increased cerebral blood flow and stroke protection, Stroke, 36, 2251, 10.1161/01.STR.0000181077.84981.11 Toshima, 2000, A new model of cerebral microthrombosis in rats and the neuroprotective effect of a Rho-kinase inhibitor, Stroke, 31, 2245, 10.1161/01.STR.31.9.2245 Shibuya, 2005, Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial, J. Neurol. Sci., 238, 31, 10.1016/j.jns.2005.06.003 Zhang, 2008, Effect of fasudil on hemorheology in patients with acute ischemic stroke, Central South Pharmacy, 3, 035 Feske, 2009, Increased leukocyte ROCK activity in patients after acute ischemic stroke, Brain Res., 1257, 89, 10.1016/j.brainres.2008.12.045 Liu, 2009, Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone, Cancer Res., 69, 8742, 10.1158/0008-5472.CAN-09-1541 Li, 2006, Involvement of Rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells, FEBS Lett., 580, 4252, 10.1016/j.febslet.2006.06.056 Vishnubhotla, 2007, ROCK-II mediates colon cancer invasion via regulation of MMP-2 and MMP-13 at the site of invadopodia as revealed by multiphoton imaging, Lab. Invest., 87, 1149, 10.1038/labinvest.3700674 Itoh, 1999, An essential part for Rho-associated kinase in the transcellular invasion of tumor cells, Nat. Med., 5, 221, 10.1038/5587 Zohrabian, 2009, Rho/ROCK and MAPK signaling pathways are involved in glioblastoma cell migration and proliferation, Anticancer Res., 29, 119 Torre, 2010, Reduction of hyaluronan-CD44-mediated growth, migration, and cisplatin resistance in head and neck cancer due to inhibition of Rho kinase and PI-3 kinase signaling, Arch. Otolaryngol. Head Neck Surg., 136, 493, 10.1001/archoto.2010.25 Kamai, 2002, The rho/rho kinase pathway is involved in the progression of testicular germ cell tumour, BJU Int., 89, 449, 10.1046/j.1464-4096.2001.01920.x Kamai, 2003, Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer, Clin. Cancer Res., 9, 2632 Patel, 2012, RKI-1447 is a potent inhibitor of the rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer, Cancer Res., 72, 5025, 10.1158/0008-5472.CAN-12-0954 Shimokawa, 2005, Rho-kinase is an important therapeutic target in cardiovascular medicine, Arterioscler. Thromb. Vasc. Biol., 25, 1767, 10.1161/01.ATV.0000176193.83629.c8 Tokushige, 2007, Effects of topical administration of Y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys, Invest. Ophthalmol. Vis. Sci., 48, 3216, 10.1167/iovs.05-1617 Williams, 2011, Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension, Am. J. Ophthalmol., 152, 834, 10.1016/j.ajo.2011.04.012 Mizuno, 2007, Ocular hypotensive and neuroprotective effects of K-115, a novel Rho-kinase inhibitor, Invest. Ophthalmol. Vis. Sci., 48, 4805 Peterson, 2008, Topical administration of a novel and potent Rho kinase (ROK) inhibitor INS117548 alters the actin cytoskeleton, effectively lowers IOP, and is well tolerated on the ocular surface, Invest. Ophthalmol. Vis. Sci., 49, 3816 Chen, 2011, Novel ocular antihypertensive compounds in clinical trials, Clin. Ophthalmol., 5, 667, 10.2147/OPTH.S15971 Lord-Fontaine, 2008, Local inhibition of Rho signaling by cell-permeable recombinant protein BA-210 prevents secondary damage and promotes functional recovery following acute spinal cord injury, J. Neurotrauma, 25, 1309, 10.1089/neu.2008.0613 Van de Velde, 2012, Topical application of AMA0076, a locally acting rho kinase (ROCK) inhibitor, results in a robust IOP control in Dutch Belted Rabbits, Acta Ophthalmol., 90, s249, 10.1111/j.1755-3768.2012.4656.x Schröter, 2008, Detection of myosin light chain phosphorylation – a cell-based assay for screening Rho-kinase inhibitors, Biochem. Biophys. Res. Commun., 374, 356, 10.1016/j.bbrc.2008.07.028 Feng, 2008, Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors, J. Med. Chem., 51, 6642, 10.1021/jm800986w Pireddu, 2012, Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2), MedChemComm, 3, 699, 10.1039/c2md00320a Chen, 2008, Chroman-3-amides as potent Rho kinase inhibitors, Bioorg. Med. Chem. Lett., 18, 6406, 10.1016/j.bmcl.2008.10.080 Sessions, 2008, Benzimidazole- and benzoxazole-based inhibitors of Rho kinase, Bioorg. Med. Chem. Lett., 18, 6390, 10.1016/j.bmcl.2008.10.095 Yin, 2010, Discovery of potent and selective urea-based ROCK inhibitors and their effects on intraocular pressure in rats, ACS Med. Chem. Lett., 1, 175, 10.1021/ml1000382 Fang, 2011, Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors, Bioorg. Med. Chem. Lett., 21, 1844, 10.1016/j.bmcl.2011.01.039 Yin, 2013, Synthesis and biological evaluation of urea derivatives as highly potent and selective Rho kinase inhibitors, J. Med. Chem., 56, 3568, 10.1021/jm400062r Davis, 2010, Benzothiophene containing Rho kinase inhibitors: efficacy in an animal model of glaucoma, Bioorg. Med. Chem. Lett., 20, 3361, 10.1016/j.bmcl.2010.04.020 Henderson, 2010, 2,3-Diaminopyrazines as rho kinase inhibitors, Bioorg. Med. Chem. Lett., 20, 1137, 10.1016/j.bmcl.2009.12.012 Ray, 2011, Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors, Bioorg. Med. Chem. Lett., 21, 97, 10.1016/j.bmcl.2010.11.060 Van de Velde, 2011, Topical application of AMA0076, a locally acting rho kinase (ROCK) inhibitor, results in a robust IOP control in a hypertensive rabbit model, Acta Ophthalmol., 89, s248, 10.1111/j.1755-3768.2011.3323.x van de Velde, 2013, 24h IOP control by subchronic AMA0076 administration in Dutch Belted rabbits, Acta Ophthalmol, 91, s252, 10.1111/j.1755-3768.2013.4224.x Gong, 2010, Integration of virtual screening with high-throughput screening for the identification of novel Rho-kinase I inhibitors, J. Biotechnol., 145, 295, 10.1016/j.jbiotec.2009.12.003 Shen, 2013, Discovery of Rho-kinase inhibitors by docking-based virtual screening, Mol. Biosyst., 9, 1511, 10.1039/c3mb00016h Shen, 2013, Discovery and optimization of triazine derivatives as ROCK1 inhibitors: molecular docking, molecular dynamics simulations and free energy calculations, Mol. Biosyst., 9, 361, 10.1039/c2mb25408e Ying, 2006, The Rho kinase inhibitor fasudil inhibits tumor progression in human and rat tumor models, Mol. Cancer Ther., 5, 2158, 10.1158/1535-7163.MCT-05-0440