qHTS to Identify Activators and Inhibitors of Wip1

National Center For Advancing Translational Sciences

Investigators

Abstract

The overall objective of this project is to develop potent, selective, and bioactive small molecule modulators of Wip1 for use as chemical probes and starting points for therapeutic development. During this period, the project team performed high-throughput screening against NCATS annotated libraries and diverse chemical library using a RapidFire mass spectrometry assay. The primary screening hits were further evaluated by a variety of additional assays to characterize their activities, including fluorescence reporter orthogonal assay, and binding studies by surface plasmon resonance (SPR). Currently powder order has been placed for the top ranking chemotypes/singletons and additional efforts have focused on detailed mechanistic studies of the enzymes mechanism of action, which could be exploited during medicinal chemistry optimization of chemical leads.