In a recent paper, we analyzed 66 published clinical candidates and traced the origins of those candidates to the initial hit, in what we termed as the “hit-to-clinical” pair.  In this presentation, we have updated the list to include &gt;100 hit-to-clinical pairs from 2016-present.  We have categorized these pairs by lead generation strategy, such as starting points derived from previously known compounds, random high throughput screening, focused screening, structure-based drug design, fragment-based lead generation, and DNA-encoded library screening (DEL), and determined that most clinical candidates are still derived from previously known examples (&gt;30%).  An analysis of physicochemical properties on the hit-to-clinical pairs was also conducted and it was determined that on average increase in molecular weight occurs from hit to clinical pair, (ΔMW = +85) but little change in lipophilicity (ΔclogP = −0.2), although exceptions are noted and discussed.  We will discuss the implications of this data and how it may impact hit finding strategies for drug discovery.

Hit generation strategies and molecular profiles of recent hit-to-clinical pairs

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