Rho-kinase Inhibitors: Small Molecules and Peptides

Rho-kinases, also known as Rho-associated coiled-coil kinases or ROCK inhibitors (ROCK), are serine/threonine kinases named for their activation by RhoA GTPases. These enzymes play a role as regulators of cytoskeletal rearrangement, including the formation of focal adhesions, cell motility, and the invasion of tumor cells. ROCK inhibitors such as Y-27632 are used in stem cell research protocols, including cell proliferation and differentiation.

There are two isoforms of Rho-kinase, namely ROCK1 (also known as ROKβ or p160 ROCK) and ROCK2 (also known as ROKα). These isoforms exhibit a significant structural similarity in their kinase domains (92%). Despite this similarity, they differ in their tissue expression patterns; ROCK2 is prominently expressed in the brain and muscle, while ROCK1 is distributed widely across various tissues. Subcellularly, ROCK2 is located in the cytosol and relocates to the cleavage furrow during cytokinesis. In contrast, ROCK1 is thought to co-localize with centrosomes, playing a crucial role in cell cycle regulation.