Structure-based development of target-specific compound libraries

• Published in: Drug discovery today Vol. 11; no. 5-6; pp. 261 - 266
• Main Authors: Orry, Andrew J.W., Abagyan, Ruben A., Cavasotto, Claudio N.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-03-2006; Elsevier Science
• Subjects: Binding Sites; Biological and medical sciences; compound library design; Computational Biology; crystallography; Crystallography, X-Ray; Databases, Protein; Drug Design; drug discovery; fragment-based; General pharmacology; ligand docking; Ligands; Magnetic Resonance Spectroscopy; Medical sciences; Models, Molecular; NMR; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Proteins - chemistry; Receptors, Cell Surface - chemistry; screening; Structure-Activity Relationship; structure-based; Biotechnology; ligand docking; NMR; crystallography; screening; compound library design; fragment-based; structure-based; Drug Discovery; Drug; Target; Specificity; Pharmaceutical technology; Databank; Chemical structure
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/S1359-6446(05)03717-7

The discovery of new therapeutics can be expedited by the design of structure-based, target specific libraries that can save time and money and can also lead to the discovery of ligands with higher potency and selectivity.
The success or failure of a small-molecule drug discovery project ultimately lies in the choice of the scaffolds to be screened – chosen from among the many millions of available compounds. Therefore, the methods used to design compound screening libraries are key for the development of new drugs that target a wide range of diseases. Currently, there is a trend towards the construction of receptor-structure-based focused libraries. Recent advances in high-throughput computational docking, NMR and crystallography have facilitated the development of these libraries. A structure-based target-specific library can save time and money by reducing the number of compounds to be experimentally tested, also improving the drug discovery success rate by identifying more-potent and specific binders.