Recent progress in fragment-based lead discovery.

Fragment-based methods have emerged as a new strategy for drug discovery. The main advantages are that useful starting points for lead identification for most targets can be identified from a relatively small (typically 1000-member) library of low molecular weight compounds. The main constraints are the need for a method that can reliably detect weak binding and strategies for evolving the fragments into larger lead compounds. The approach has been validated recently as series of compounds from various programs have entered clinical trials. Current new developments are focussing on application of the methods to targets where conventional HTS fails and to integration of fragments alongside HTS for more druggable targets. Here, we provide a brief summary of the key elements of fragment-based lead discovery (FBLD), review recent progress and provide a perspective on the challenges that remain for the field.

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