Leah N. Makley and Jason E. Gestwicki Expanding the Number of ‘Druggable’ Targets: Non-Enzymes and Protein–Protein Interactions Chemical Biology & Drug Design 81
In this review, we discuss methods for discovering drugs that inhibit traditionally ‘undruggable’ targets, such as non-enzymes that use protein-protein interactions to engage in pathobiology. This issue is increasingly important in a post-genomic era because predicted drug targets often arise from molecular biology-based approaches. Accordingly, new methods of high-throughput screening and computational prediction are needed to uncover ligands for non-enzymes. Additionally, new chemical libraries are needed that enrich for the specific physicochemical features that are required to block protein-protein interactions.
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