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. 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. More recently they have been studied for the treatment of glaucoma and as a therapeutic target for the treatment of cardiovascular diseases, including ischemic stroke. While statin therapy has been demonstrated to reduce the risk of major cardiovascular events, including ischemic stroke, the interplay between the ROCK pathway and statin therapy to treat and prevent strokes in older adults has not yet been proven.
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. Particularly, ROCK inhibitor is used for cell culture practice, in part to limit cellular death and limited dedifferentiation, and therefore widely adopted for induced pluripotent stem cells (iPSC) and embryonic stem cell cultures, although studies have shown mixed results for other cells types.
Molecular mechanism.
Rho kinase inhibitors act on Rho kinase by altering the conformation of the protein, disrupting translocation to the plasma membrane, preventing ATP-dependent phosphorylation, and blocking RhoA binding to ROCK. Some studies suggest that Rho kinase inhibitors also play a role in anti-angiogenesis by blocking ERK and Akt signaling pathways. Rho kinase inhibitor also functions by blocking rho-mediated dephosphorylation of MLC20.
Examples.
A number of Rho kinase inhibitors are known.
References.
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