New Modalities, Technologies, and Partnerships in Probe and Lead Generation: Enabling a Mode-of-Action Centric Paradigm

With the rise of novel biology and high potential target identification technologies originating from advances in genomics, medicinal chemistsare progressively facing targets of increasing complexity and often unprecedented. Novel hit finding technologies, combined with a wider choice of drug modalities, has resulted in a unique repertoire of options to address these challenging targets and to identify suitable starting points for optimization. Furthermore, innovative solutions originating from a range of academic groups and biotech companies require new types of collaborative modelsto leverage and integrate them in the drug discovery process. This perspective provides a guide for medicinal chemistscovering contemporary probe and lead generation approaches and discusses the strengths and limitations of each strategy. Moreover, the expansion of strategies to modulate proteins creates the opportunity of a modality-agnostic and mode-of-action centric hit finding paradigm.