Rho kinase (also known as P160ROCK, Rho-activated kinase) is activated by members of the Rho small G protein family, which are activated by GTP exchange factors, such as ARHGEF1 (Q92888, p115-RhoGEF), which in turn may be activated by Gα_12/13 subunits [4].

* Key recommended reading is highlighted with an asterisk

* Abedi F, Hayes AW, Reiter R, Karimi G. (2020) Acute lung injury: The therapeutic role of Rho kinase inhibitors. Pharmacol Res, 155: 104736. [PMID:32135249]

Feng Y, LoGrasso PV, Defert O, Li R. (2016) Rho Kinase (ROCK) Inhibitors and Their Therapeutic Potential. J Med Chem, 59 (6): 2269-300. [PMID:26486225]

Nishioka T, Shohag MH, Amano M, Kaibuchi K. (2015) Developing novel methods to search for substrates of protein kinases such as Rho-kinase. Biochim Biophys Acta, 1854 (10 Pt B): 1663-6. [PMID:25770685]

* Sharma P, Roy K. (2020) ROCK-2-selective targeting and its therapeutic outcomes. Drug Discov Today, 25 (2): 446-455. [PMID:31837997]

Shimokawa H, Sunamura S, Satoh K. (2016) RhoA/Rho-Kinase in the Cardiovascular System. Circ Res, 118 (2): 352-66. [PMID:26838319]

1. Bosanac T, Hickey ER, Ginn J, Kashem M, Kerr S, Kugler S, Li X, Olague A, Schlyer S, Young ER. (2010) Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 3, aryl substituted pyrrolidines. Bioorg Med Chem Lett, 20 (12): 3746-9. [PMID:20471253]

2. Chen YT, Vojkovsky T, Fang X, Pocas JR, Grant W, Handy AMW, Schroter T, LoGrasso P, Bannister TD, Feng Y. (2011) Asymmetric synthesis of potent chroman-based Rho kinase (ROCK-II) inhibitors. Medchemcomm, 2: 73-75.

3. Doe C, Bentley R, Behm DJ, Lafferty R, Stavenger R, Jung D, Bamford M, Panchal T, Grygielko E, Wright LL et al.. (2007) Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther, 320 (1): 89-98. [PMID:17018693]

4. Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC. (1998) p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13. Science, 280 (5372): 2109-11. [PMID:9641915]

5. Löhn M, Plettenburg O, Ivashchenko Y, Kannt A, Hofmeister A, Kadereit D, Schaefer M, Linz W, Kohlmann M, Herbert JM et al.. (2009) Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension, 54 (3): 676-83. [PMID:19597037]

6. Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schönbrunn E, Sebti SM et al.. (2012) Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm, 3 (6): 699-709. [PMID:23275831]

7. Ray P, Wright J, Adam J, Bennett J, Boucharens S, Black D, Cook A, Brown AR, Epemolu O, Fletcher D et al.. (2011) Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors. Bioorg Med Chem Lett, 21 (1): 97-101. [PMID:21145740]

8. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M et al.. (1997) Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature, 389 (6654): 990-4. [PMID:9353125]

9. Wu F, Büttner FH, Chen R, Hickey E, Jakes S, Kaplita P, Kashem MA, Kerr S, Kugler S, Paw Z et al.. (2010) Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account. Bioorg Med Chem Lett, 20 (11): 3235-9. [PMID:20462760]