Abstract:
Recently discovered cellular target engagement technologies such as the cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and thermal proteome profiling (TPP) are quickly impacting the ways in which drug discovery scientists identify and validate new drugs. With an expanding repertoire of available techniques, target engagement assays enable one to determine if their inhibitors reach their intended targets in cells and tissues with unprecedented accuracy. As a result, implementing these chemical biology techniques into the drug discovery process is quickly becoming an essential component of medicinal chemistry research programs.
In this context, I will introduce ongoing research project in the Page Lab, which focus on applying state of the art chemical biology techniques within the drug discovery process. This will include exploring the use of CETSA to identify inhibitors of NUDT5 protein, an important target mediating hormone signaling in breast cancer cells. As well, I will describe two projects where we have identified the direct molecular targets for hit compounds from high-throughput phenotypic screening campaigns, and highlight how we have used these as chemical probes to learn more about cancer cell biology.