The ultimate goal of an experimental lead finding campaign is to produce a dataset of sufficient breadth and quality to justify and focus medicinal chemistry resources on developing early lead series.  The utilization of a variety of biophysical techniques in lead finding has been on the rise.  Due to limited throughput compared to modern HTS infrastructure biophysical assessment has tended to be limited to later stages of hit characterization and the screening of small libraries.  Through refinement of our methodology and the advancement of modern optical biosensor hardware and software we have been able to provide biophysical assessment of HTS hits during the HTS screening cascade, rather than later in hit triage or after repurchase/resynthesis.  In addition we are utilizing the non-enzymatic nature of the sensor to provide rapid mechanism of action assessment on larger numbers of both HTS and fragment screening hits, which can be useful in situations where MOA by biochemical approaches can be technically challenging.  We are also using new cheminformatic tools to cluster fragments by their properties in addition to chemical structure, and provide chemists with a  preliminary priority score based on a variety of properties.  Through tighter and more coordinated multidisciplinary efforts we are continuing to find ways to enhance confidence and understanding of hits emerging from different lead generation platforms.

How do you know what you know: Modern developments in biophysical hit assessment to enhance confidence in the output of lead generation campaigns

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.