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Targeting protein-protein interactions for therapeutic intervention: a challenge for the future Zinzalla G; Thurston DEFuture Med Chem 2009[Apr]; 1 (1): 65-93BACKGROUND: Over the last two decades, an increasing research effort in academia and industry has focused on the modulation (both inhibition and stabilization) of protein-protein interactions (PPIs) in order to develop novel therapeutic approaches and target-selective agents in drug discovery. DISCUSSION: The diversity and complexity of highly dynamic systems such as PPIs present many challenges for the identification of drug-like molecules with the ability to modulate the PPI with the necessary selectivity and potency. In this review, a number of these strategies will be presented along with a critical overview of the challenges and potential solutions relating to the exploitation of PPIs as molecular targets. CONCLUSIONS: Both traditional drug discovery approaches and some more recently developed innovative strategies have already provided valuable tools for the discovery of PPI modulators, and a number of successful examples have highlighted the potential of targeting PPIs for therapeutic intervention, especially in the oncology area.|*Drug Design[MESH]|Allosteric Regulation[MESH]|Biological Products/chemistry/pharmacology[MESH]|High-Throughput Screening Assays[MESH]|Protein Interaction Domains and Motifs/drug effects[MESH]|Proteins/*antagonists & inhibitors/metabolism[MESH]|Small Molecule Libraries/chemistry/pharmacology[MESH] |
