Translational Biomedicine

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Targeting Cancer Cells During Mitosis Using Novel S-Trityl-LCysteine(STLC) Analogs

Ashish Ravindra Patil

The design of synthetic small molecules that target cytoskeleton microtubule is important for the investigation of the mechanism of cell division and for the development of novel anti-tumor agents. Molecules targeting microtubule stability such as Taxanes and Vinca alkaloids are among the most successful anticancer agents. However, such molecules cause undesired side effects, including neurotoxicity, and are subject to acquired drug resistance. In 1999, researchers discovered a completely new target for anti-mitotic activity is the microtubuleassociated kinesin Eg5 (kinesin spindle protein, KSP). Eg5 is a member of the kinesin-5 family and plays an important role in the early stages of mitosis. Specifically, kinesin Eg5 plays an important role in bipolar spindle formation. Inhibition of this motor protein leads to the formation of monopolar spindles, mitotic arrest, followed by cell apoptosis. Molecules targeting KSP selectively act only on the cells undergoing cell division, making them mitosis-specific drugs. S-trityl-L-cysteine (STLC) is a potent allosteric inhibitor of kinesin spindle protein (KSP); however, this compound has limited potential use for cancer treatment due to its amphiphilic and poor drug-like characteristics.