Rho kinase inhibitor

Rho-kinase inhibitors (rho-associated protein kinase inhibitor or ROCK inhibitor) are a series of compounds that target rho kinase (ROCK) and inhibit the ROCK pathway.[1] Clinical trials have found that inhibition of the ROCK pathway contributes to the cardiovascular benefits of statin therapy. Furthermore, ROCK inhibitors may have clinical applications for anti-erectile dysfunction, antihypertension, and tumor metastasis inhibition.[2] More recently they have been studied for the treatment of glaucoma[3] and as a therapeutic target for the treatment of cardiovascular diseases, including ischemic stroke.[4] While statin therapy has been demonstrated to reduce the risk of major cardiovascular events, including ischemic stroke,[5] the interplay between the ROCK pathway and statin therapy to treat and prevent strokes in older adults has not yet been proven.[4]

On a cellular level, ROCK has multiple functions, including regulation of smooth muscle cell contraction, cell migration, and maintenance of cell viability and morphology, in part by regulating stress fibers and focal adhesions.[2] Particularly, ROCK inhibitor is used for cell culture practice, in part to limit cellular death and limited dedifferentiation,[6][7][8] and therefore widely adopted for induced pluripotent stem cells (iPSC) and embryonic stem cell cultures,[9] although studies have shown mixed results for other cells types.[10]

ROCK Inhibitor Pathway
  1. ^ Liao, James K.; Seto, Minoru; Noma, Kensuke (July 2007). "Rho Kinase (ROCK) Inhibitors". Journal of Cardiovascular Pharmacology. 50 (1): 17–24. doi:10.1097/FJC.0b013e318070d1bd. ISSN 0160-2446. PMC 2692906. PMID 17666911.
  2. ^ a b Liao JK, Seto M, Noma K (July 2007). "Rho kinase (ROCK) inhibitors". Journal of Cardiovascular Pharmacology. 50 (1): 17–24. doi:10.1097/FJC.0b013e318070d1bd. PMC 2692906. PMID 17666911.
  3. ^ Wang SK, Chang RT (2014). "An emerging treatment option for glaucoma: Rho kinase inhibitors". Clinical Ophthalmology. 8: 883–90. doi:10.2147/OPTH.S41000. PMC 4025933. PMID 24872673.
  4. ^ a b Sladojevic N, Yu B, Liao JK (December 2017). "ROCK as a therapeutic target for ischemic stroke". Expert Review of Neurotherapeutics. 17 (12): 1167–1177. doi:10.1080/14737175.2017.1395700. PMC 6221831. PMID 29057688.
  5. ^ O'Brien EC, Greiner MA, Xian Y, Fonarow GC, Olson DM, Schwamm LH, et al. (October 2015). "Clinical Effectiveness of Statin Therapy After Ischemic Stroke: Primary Results From the Statin Therapeutic Area of the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study". Circulation. 132 (15): 1404–13. doi:10.1161/CIRCULATIONAHA.115.016183. PMID 26246175. S2CID 11252336.
  6. ^ Matsumoto E, Furumatsu T, Kanazawa T, Tamura M, Ozaki T (March 2012). "ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes". Biochemical and Biophysical Research Communications. 420 (1): 124–9. doi:10.1016/j.bbrc.2012.02.127. PMID 22405765.
  7. ^ Furumatsu T, Matsumoto-Ogawa E, Tanaka T, Lu Z, Ozaki T (April 2014). "ROCK inhibition enhances aggrecan deposition and suppresses matrix metalloproteinase-3 production in human articular chondrocytes". Connective Tissue Research. 55 (2): 89–95. doi:10.3109/03008207.2013.852544. PMID 24111521. S2CID 41211282.
  8. ^ Qi Y, Liang X, Dai F, Guan H, Sun J, Yao W (July 2020). "RhoA/ROCK Pathway Activation is Regulated by AT1 Receptor and Participates in Smooth Muscle Migration and Dedifferentiation via Promoting Actin Cytoskeleton Polymerization". International Journal of Molecular Sciences. 21 (15): 5398. doi:10.3390/ijms21155398. PMC 7432407. PMID 32751352.
  9. ^ Claassen DA, Desler MM, Rizzino A (August 2009). "ROCK inhibition enhances the recovery and growth of cryopreserved human embryonic stem cells and human induced pluripotent stem cells". Molecular Reproduction and Development. 76 (8): 722–32. doi:10.1002/mrd.21021. PMC 3257892. PMID 19235204.
  10. ^ Nukaga T, Sakai D, Schol J, Suyama K, Nakai T, Hiyama A, Watanabe M (2019). "Minimal Sustainability of Dedifferentiation by ROCK Inhibitor on Rat Nucleus Pulposus Cells In Vitro". Spine Surgery and Related Research. 3 (4): 385–391. doi:10.22603/ssrr.2019-0019. PMC 6834460. PMID 31768460.