Validate target engagement early
in drug discovery

Hit compounds worth pursuing

A major challenge in evaluating hits is to select hit compounds worth pursuing as a chemical scaffold during drug discovery. The success of HTS campaigns depends on post-screen hit-triaging , because of undesired compound-assay interference leading to false-positive data. These could be categorized into technical false-positives (e.g. quenchers, auto-fluorescence, inhibitors of secondary enzymatic reactions) and hits with undesired modes-of-action (chelators, aggregators, redox, etc.). Thus, a comprehensive hit triaging cascade of assays including counter-screening, deselection, orthogonal, selectivity as well as target engagement biophysical assays such as TSA, MST, ITC, SPR are required. 

Follow-up assays are either dependent on fluorescent labels and therefore minimally de-risk the identified hits or require large amounts of reagents and are generally low in throughput and laborious. The hit confirmation phase of a conventional drug discovery project requires ~1.5 years. The above-mentioned secondary assays tailored for the project requirements also drive about 85% of the cost of hit confirmation.