KIF1C Inhibitors

Chemical inhibitors of KIF1C can exert their inhibitory effects through various modes of action that target the motor domain of the protein, which is crucial for its ATPase activity and microtubule-dependent motility. Monastrol is one such inhibitor that specifically binds to this domain, resulting in the cessation of ATPase activity and, subsequently, the microtubule-dependent movement that is characteristic of KIF1C's function. Similarly, Ispinesib and Filanesib effectively target the motor domain; Ispinesib by selective binding that hinders ATPase activity and impairs mitotic functions, and Filanesib by allosteric interactions that disrupt microtubule interactions and inhibit cell division roles of KIF1C. Kif15-IN-1 also targets the motor domain but does so by hindering ATP-binding capability, leading to the direct inhibition of motor activity. Paprotrain follows a similar inhibition pathway by binding to the motor domain, resulting in the direct halt of ATPase activity and microtubule movement. Further along these lines, CW069 interacts with allosteric sites of KIF1C, diminishing its microtubule association and motor function. Kif18a-IN-1 inhibits KIF1C by binding to the motor domain; it competes for the ATP-binding site, affecting both ATPase and microtubule dynamics activities. K858, another selective inhibitor, competes with ATP at the motor domain, inhibiting microtubule-mediated transport. Dimethylenastron and MPI-0479605 both target ATP binding and hydrolysis in the motor domain, leading to inhibited motor activity and transport functions. Lastly, S-Trityl-L-cysteine binds to the motor domain, similar to other inhibitors, but its specific action inhibits ATPase activity, thereby stalling the microtubule-stimulated movement of KIF1C. Each of these chemicals directly impacts the motor activity of KIF1C by targeting its ATPase function or microtubule interaction, resulting in the inhibition of the protein's intrinsic motor functions.