USING SMALL MOLECULES TO IDENTIFY NOVEL ANTI-CANCER TARGETS

The underlying goal of Professor Hergenrother’s research is to identify novel biological macromolecules that can be targeted for the treatment of a variety of disease states. Specifically, he focuses on understanding the molecular basis of diseases in which cell death is regulated aberrantly (e.g., cancer, neurodegenerative disorders, multidrug-resistant bacterial infections). He probes these aberrations at the molecular level by synthesizing and identifying novel organic compounds that strongly and selectively bind to individual biological targets, then applying these compounds in vivo to elucidate the role of individual proteins implicated in a variety of disorders. This effort involves techniques from a number of disciplines, including synthetic organic chemistry, combinatorial chemistry, molecular and cell biology, high-throughput screening, and biological assay development.

During his Center appointment, Professor Hergenrother and coworkers will follow up on an exciting result from his laboratory that was reported in December 2003: A compound dubbed 13-D was found to induce the selective process of programmed death in cancer cells. Although the result is quite provocative, the underlying molecular basis remains to be elucidated. To learn more, they will synthesize a series of specially designed 13-D analogues and use them in a variety of biochemical experiments. Determining precisely the molecular target of 13-D could pave the way for a new generation of nontoxic anticancer drugs.