neuronal kinesin heavy chain Inhibitors

Chemical inhibitors of neuronal kinesin heavy chain can disrupt the protein's function by various mechanisms, all of which involve the inhibition of ATPase activity that is crucial for the motor function of this protein. Monastrol, a known Eg5 inhibitor, can bind to the motor domain of neuronal kinesin heavy chain, obstructing the ATPase activity that powers the protein's movement along microtubules. Similarly, Ispinesib and Filanesib, both selective inhibitors of kinesin spindle proteins, can attach to the motor domain of neuronal kinesin heavy chain, preventing ATP turnover and effectively inhibiting the transport function of the protein. Dimethylenastron, by binding to the same motor domain of Eg5, can inhibit the ATP hydrolysis mechanism that is essential for the anterograde transport carried out by neuronal kinesin heavy chain.

Additional chemical inhibitors such as CW069 and Kif15-Inhibitor can interfere with the conformation and ATPase activity of neuronal kinesin heavy chain. CW069 achieves this through allosteric inhibition, altering the conformation of the motor domain and thereby inhibiting the motor activity of the protein. On the other hand, Kif15-Inhibitor binds directly to the motor domain to hinder ATP hydrolysis. Paprotrain, a selective inhibitor of the mitotic kinesin MCAK, can block the ATPase activity of neuronal kinesin heavy chain by a similar mechanism, thus inhibiting its function. S-Trityl-L-cysteine, another Eg5 inhibitor, can also inhibit the neuronal kinesin heavy chain by binding to its motor domain and obstructing ATPase activity. AZ82, designed to inhibit Eg5, can bind to the motor domain of neuronal kinesin heavy chain, preventing ATP turnover. FTI-277, although not a direct inhibitor of the motor domain, can inhibit the function of neuronal kinesin heavy chain by disrupting necessary post-translational modifications that are essential for the proper localization and function of the protein. Lastly, GSK923295, an inhibitor of CENP-E kinesin motor activity, can bind to the motor domain and inhibit ATPase activity, which is a shared characteristic with neuronal kinesin heavy chain, thereby affecting the protein's transport capabilities.