Hsp90 (Heat-shock protein 90) plays a key role in regulating the physiology of cells exposed to environmental stress and in maintaining the malignant phenotype of tumor cells. Cancer cells grow in an environment of hypoxia, low pH, and low-nutrient concentration.
In our initial studies, we, in collaboration with Dr. Gabriela Chiosis, have designed structures to bind the Hsp90 alpha ATP/ADP-binding site. The first designed derivative, PU3, showed a good theoretical fit and fulfilled all of the important interactions with the protein pocket.
Src kinase activity is elevated in some human tumors, including breast and colon cancer. The activity of src plays a role in cell proliferation and transformation. We are studying the activities of a kinase inhibitor, which shows selectivity toward the src family protein kinases.