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 ( 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 Applications

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44GM058976-03
Application #
6386410
Study Section
Special Emphasis Panel (ZRG1-SSS-I (01))
Program Officer
Preusch, Peter C
Project Start
1999-04-01
Project End
2004-06-30
Budget Start
2001-07-01
Budget End
2004-06-30
Support Year
3
Fiscal Year
2001
Total Cost
$369,725
Indirect Cost
Name
Cytoskeleton
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206