Research Project
2792658
Eukaryotic kinesin motor proteins utilize the energy of ATP hydrolysis to move cargoes, such as chromosomes and vesicles, along cytoskeletal microtubule networks. They play a major role in almost all aspects of intracellular transport and are involved in a wide range of physiological processes, including embryonic development, axonal transport, exocytosis, endocytosis and cell division. The essential role of many kinesins in cell division, and the fact that overexpression of kinesins have been linked to cancers such as retinoblastomas, make them very attractive targets for the development of anti-mitotics. The observation that many kinesins are expressed exclusively during cell division also suggests that they may be superior to current anti-mitotic drug targets such as the ubiquitously expressed tubulins. In Phase I of this proposal we developed a highly robust, sensitive and cost effective HTS assay capable of identifying compounds that can modulate kinesin activity (see Phase I report). In this Phase II application, we intend to expand our HTS screen to include a representative panel of kinesin proteins. We propose to utilize the assay to screen a compound library with the purpose of identifying kinesin specific anti-mitotic compounds. Such compounds are predicted to be clinically relevant in a wide range of diseases including cancers and fungal infections. It is also anticipated that these compounds will be invaluable research tools. PROPOSED COMMERCIAL APPLICARION Commercial application is in three areas: First in drug development and partnership with pharmaceuticals companies. Second, through sales of the high through-put screens, and third, through the sales of compounds and proteins for basic research.
