SBIR Phase I: Development of a conformational screen for rapidly identifying kinase inhibitor type using SHG

This Small Business Innovation Research (SBIR) Phase I project builds on the rapid FDA approval success of recent cancer therapeutics that act on a specific conformation state of their target protein. Biodesy has developed a new optical technique, Second Harmonic Generation that measures protein conformation in real time and addresses the challenge of rapidly identifying and discriminating ligands that bind to or induce different protein conformations. They are applying this technique to understanding the critical protein conformations that distinguish the different classes of inhibitors against protein kinases. Biodesy plan to use site-specific mutations of cysteines within Abl kinase to identify and measure conformation changes at discrete areas within the protein and study how these are modified in the presence and absence of different classes of inhibitors. The broader/commercial implications of this research are to provide a comprehensive, high throughput platform that will enable the rapid identification of novel therapeutics. The FDA recently provided accelerated approval to a structure-specific inhibitor of BRaf, Vemurafenib, which functions by holding its targeted protein in an inactive conformation state. Gleevec (revenue in excess of $4B), functions in a similar fashion. Interest in techniques that can identify this mechanism of action has grown markedly. Biodesy?s platform has the potential to greatly accelerate identification and development of similar therapeutics. There are more than 500 kinases in the kinome so the commercial potential of the approach is significant. Furthermore, its broader impact is to provide a general method for identifying conformation-specific drugs across all target classes.