Scientific Report 2007

Scripps Florida

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Translational Research Institute

Development of Protein Kinase Inhibitors

C. Liang, M. Koenig, P. Holmberg, Y. He

Our goal is to discover protein kinase inhibitors that can be used as therapeutic agents for the treatment of human diseases such as cancer and arthritis. Protein kinases are a class of enzymes that catalyze the transfer of the γ -phosphate from ATP to protein substrates. These enzymes play critical roles in signal transduction for a number of cellular functions. In particular, they regulate most of the hallmarks of cancer: cell proliferation, cell survival, cell motility/metastasis, cell cycle/division, and angiogenesis. Protein kinases are also implicated in inflammatory diseases such as arthritis and asthma. For these reasons, protein kinases are being investigated as valuable therapeutic targets by almost every pharmaceutical company, and according to estimates, about 25% of all current pharmaceutical research is devoted to these targets.

In the past year, we successfully completed the first drug discovery project in collaboration with Poniard Pharmaceuticals (formerly NeoRx Corporation), Seattle, Washington. The collaboration was then expanded to include D.D. Schlaepfer, Department of Immunology. Our goal was to identify lead compounds that would inhibit focal adhesion kinase. By April, we had exceeded the original goal; we have identified novel compounds with excellent potency and oral bioavailability. Preclinical studies are under way to identify potential clinical candidates. Provisional patent applications have been filed.