Increasing the delivery of next generation therapeutics from high throughput screening libraries

•Next generation therapeutics rely on understanding how to use diversity libraries.•Small ligand efficient molecules potentially offer the best starting points for drug design.•These compounds are often missed by conventional screening processes.•Increased screening concentrations rescues these valuable starting points.•Artefacts can be managed without swamping hit analysis.

The pharmaceutical industry has historically relied on high throughput screening as a cornerstone to identify chemical equity for drug discovery projects. However, with pharmaceutical companies moving through a phase of diminished returns and alternative hit identification strategies proving successful, it is more important than ever to understand how this approach can be used more effectively to increase the delivery of next generation therapeutics from high throughput screening libraries.There is a wide literature that describes HTS and fragment based screening approaches which offer clear direction on the process for these two distinct activities. However, few people have considered how best to identify medium to low molecular weight compounds from large diversity screening sets and increase downstream success.