A new era for microcalorimetry in drug development

The binding affinity is determined by enthalpic and entropic forces. In the past, structure activity relationships (SAR) aimed at improving the affinity of potential drug candidates have been hampered by the absence of information regarding the origin of specific advantageous or detrimental effects, and consequently the absence of clear guidelines for optimization. New developments relate specific ligand/target interactions and chemical modifications to their impact on the enthalpy and entropy of binding. ITC directly measures the enthalpic and entropic contributions to binding, thus providing a unique window into the forces that determine the binding for specific ligands. New ITC instrumental developments, on the other hand, offer the unique opportunity of characterizing a wide array of potential drug candidates, not only in terms of their binding affinity but also their binding enthalpy and entropy. These added dimensions can be expected to tremendously accelerate the drug development process.