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J Med Chem. 2018 Oct 25;61(20):9004-9029. doi: 10.1021/acs.jmedchem.8b00378. Epub 2018 Jun 13.

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

Author information

1
Medicinal Chemistry, Cardiovascular, Renal and Metabolism, IMED Biotech Unit , AstraZeneca , Pepparedsleden 1 , Mölndal 431 83 , Sweden.
2
External Innovation Drug Discovery, Global Business Development & Licensing , Sanofi , 13 quai Jules Guesde , 94400 Vitry-sur-Seine , France.

Abstract

With the rise of novel biology and high potential target identification technologies originating from advances in genomics, medicinal chemists are 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 models to leverage and integrate them in the drug discovery process. This perspective provides a guide for medicinal chemists covering 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.

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