Choosing lead generation strategy is one of the most important decisions in drug discovery projects. An overview of what strategies have been successful in identifying small molecule candidate drugs will be presented. To find this information (a set of clinical candidates and their respective original hit), recent Journal of Medicinal Chemistry articles were scrutinized. We observe that most candidate drugs come from known starting points (43%). For targets, where there’s little information, it is reassuring to be able to show that HTS delivers (29%). The remainder of approaches included focused screening, structure-based drug design, fragment-based lead generation, and DNA-encoded library screening. It is clear that regardless of the hit-finding strategy, the final clinical candidate is a much-improved compound compared to the initial hit. Significant effort and time in chemistry is often required which adds to MW and complexity of scaffolds. In conclusion, this study provides a retrospective analysis of past trends that have led to successful clinical candidates and hopefully provides the framework for the exploitation of future opportunities.

Where do recent candidate drugs come from?

2019 Fall National Meeting

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