Chemistry-driven target identification

Lead Generation Methods, Strategies, and Case Studies, First Edition. Edited by Jdrg Holenz. 

From a medicinal chemistry perspective, the optimization of a lead series for affinity, selectivity, and pharmacological profile is often more intuitive if the efficacy target(s) is known. This suggests that MMoA elucidation (i.e., the so-called target deconvolution or deorphaning) of the hits or leads derived from phenotypic screens can be useful both in their further development and for finding additional chemical series. 

Additionally, the discovery of novel cellular functions of proteins and pathway nodes can get around patent limitations, which hinder work on specific targets and chemotypes, and provide first-in-class new molecular entities (NME). 

Chemistry-Driven Target Discovery Enabling Biology 

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Figure 4.1 Chemistry-driven target identification by phenotypic screening fit in the drug discovery value chain (boxed). Some discovery activities could (should, whenever possible) be prosecuted in parallel.

Chemistry-Driven Target identification Table 4.2 Continued)... 

Advances in identification of therapeutic targets and medicinal chemistry to interact with these targets have driven changes in the way that toxicologists contribute to the discovery and development of drugs. The emphasis is... 

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