Myosin-13 Inhibitors

Myosin inhibitor compounds function by perturbing the actin cytoskeleton or modulating the phosphorylation state of myosin. Blebbistatin, ML-7, and Y-27632, for example, affect the state of myosin phosphorylation. By doing so, these compounds can alter the motor function of myosins, including Myosin-13, which relies on the phosphorylation state for its activity. In addition to the modulation of myosin's phosphorylation, the integrity and dynamics of the actin cytoskeleton serve as a critical determinant of myosin function. Compounds such as Latrunculin A, Cytochalasin D, and Jasplakinolide directly bind to actin, either preventing its polymerization or stabilizing the filaments, thereby influencing the physical platform upon which Myosin-13 operates. This can result in alterations to the motor activity of Myosin-13 as it engages and translocates along actin filaments.

The actin-regulating proteins are also targeted by inhibitors like CK-636 and SMIFH2, affecting the nucleation and polymerization of actin filaments, which are essential for myosin-based motility. By changing the architecture of the actin network, these inhibitors can modify the interaction between Myosin-13 and the actin filaments, impacting the force generation and movement of this motor protein. Other inhibitors work by modulating signaling pathways that indirectly affect myosin activity. For example, W-7 acts as an antagonist to calmodulin, a calcium-binding messenger protein that is involved in the regulation of myosin light chain kinase, an enzyme that phosphorylates myosins.