Objective

Differential Scanning Fluorimetry (DSF) provides a simple biophysical approach for identifying chemical equity that directly engages target proteins of interest. Here we describe its application against an Oncology target. By rapidly profiling a 50K compound subset an extensive assessment of the target’s ligandability was performed prior to initiating assay development for a full High Throughput Screen (HTS).  ~1000 hits were identified from which a small number were selected to generate a tool set. These facilitated development of several orthogonal biophysical systems required for the project (SPR, NMR and x-ray crystallography) and confirmed target engagement from the original DSF hits. This supported the decision to progress to a full HTS and cellular activity has subsequently been displayed for a number of the compounds. All this was achieved within 3 months of initiating the first protein batch grow and demonstrates the power of applying DSF early in a project’s life cycle.