This interdisciplinary project provides a unique training opportunity by including all stages of drug discovery:
- computer modeling of drug-enzyme interaction (with biophysicist Dr. Freddie Salsbury)
- chemical synthesis of candidate drugs (with chemist Dr. Mark Welker)
- in vitroandinvivotesting of synthesized drugs in mouse models of prostate cancer (with Dr. George Kulik)
The goal is to synthesize prostate tumor-specific inhibitors of signaling pathways that control BAD phosphorylation and apoptosis.
Prostate tumor specificity will be achieved by:
- generating an inactive pro-drug activated by prostate tumor-secreted protease (PSA)
- targeting pro-drug to prostate tumors by prostate-specific antibodies
Computer modeling will be used to analyze interactions between activated pro-drugs and target kinases; candidate pro-drugs selected based on this modeling will be synthesized and tested in vitro and in vivo using luminescent xenografts models of prostate cancer.