The project team aims to identify small molecule inhibitors capable of targeting the PBD domain of PLK1. Optimized compounds will be extensively profiled to identify candidates with appropriate potency, selectivity, and pharmacokinetic (PK)/pharmacodynamic (PD) profile to enable their use in both in vitro and in vivo models. During this period, the project team worked to develop cell-based assays to monitor PLK1-PBD activity in live cells, and identified small molecule hits using virtual screening. A medicinal chemistry optimization campaign is ongoing to further improve compound properties. We have adopted a cell based nanoBret assay to support currently ongoing hit optimization. A manuscript is under preparation in collaboration with Kyung Lee (NCI) and Ken Jacobson (NIDDK). Medicinal chemistry still underway to identify the probe compound which can be used in vivo study.
