Abstract

We have
compiled an Index set of ~10,000 compounds to be representative of the LifeArc
compound collection of ~150,000 small drug-like compounds, which has been
purchased over several years from a variety of commercial suppliers.  We will present a retrospective review of hit
performance for this library against multiple targets and demonstrate that
screening of the Index set is predictive of hit rates in the larger collection
and can be used as a measure of tractability of a target.  We will exemplify this with data generated
against a panel of two pore potassium channels in which 4/5 classes tested
generated hit matter with confirmed activity. The small size of the library also
makes it amenable for medium throughput screening in which complex phenotypic
assays can be profiled.  Here we compare
the performance of our Index set against a set of pharmacologically active
compounds in an imaging-based assay for aggregate clearance.  Together, these case studies exemplify the
value of the Index set for phenotypic screening and assessing target
tractability.