Adding calorimetric data to decision making in lead discovery: a hot tip

• Published in: Nature reviews. Drug discovery Vol. 9; no. 1; pp. 23 - 27
• Main Authors: Ladbury, John E, Klebe, Gerhard, Freire, Ernesto
• Format: Journal Article Book Review
• Language: English
• Published: London Nature Publishing Group UK 01.01.2010; Nature Publishing Group
• Subjects: Biomedical and Life Sciences; Biomedicine; Biotechnology; Calorimetry; Calorimetry - methods; Cancer Research; Decision Making; Drug Design; Drug Discovery - methods; Drug Industry - methods; Drug metabolism; innovation; Measurement; Medicinal Chemistry; Molecular Medicine; Pharmacology/Toxicology; Physiological aspects; Protein Binding; Thermodynamics; United States
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/nrd3054

Isothermal titration calorimetry can be used to obtain thermodynamic data on the binding of compounds to protein targets. Ladbury and colleagues propose that these data — particularly the change in enthalpy — could be a valuable addition to established tools for selecting compounds in lead discovery and for aiding lead optimization. Recognition of the limitations of high-throughput screening approaches in the discovery of candidate drugs has reawakened interest in structure-based and other rational design methods. Here, we describe how isothermal titration calorimetry can be used to obtain thermodynamic data on the binding of compounds to protein targets. We propose that these data — particularly the change in enthalpy — could provide a valuable, complementary addition to established tools for selecting compounds in lead discovery and for aiding lead optimization.