Lead-like paradigm

In a catabolic or deconstructive, process, a higher-affinity inhibitor is decomposed into fragments by retrosynthetic means. The catabolic approach is no different from typical LLDD and does not need to be evaluated here (although, as noted below, a different paradigm, ligand efficiency, is needed to drive the process forward). This is no different to what is routinely done to optimize lead-like molecules. Often it is assumed that... 

The emphasis in this contribution is laid on an emerging paradigm in drug discovery, notably the systematic classification of therapeutically relevant target classes according to structure and function. These are subsequently correlated with family-wide recognition motifs that can be translated into lead-like low-molecular-... 

This may seem like a simplistic, anti-intellectual approach to drug discovery, but it has proven to be a very successful lead discovery paradigm for decades. The scale and industrialization cf the operation often masks the incredible innovation and smart thinking that has gone into the HTS process over the last 10 years. 

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