Insight into Thermodynamic and Kinetic Profiles in Small-Molecule Optimization

Structure–activity relationships (SARs) and structure–property relationships (SPRs) have been considered the most important factors during the drug optimization process. For medicinal chemists, improvements in the potencies and druglike properties of small molecules are regarded as their major goals. Among them, the binding affinity and selectivity of small molecules on their targets are the most important indicators. In recent years, there has been growing interest in using thermodynamic and kinetic profiles to analyze ligand–receptor interactions, which could provide not only binding affinities but also detailed binding parameters for small-molecule optimization. In this perspective, we are trying to provide an insight into thermodynamic and kinetic profiles in small-molecule optimization. Through a highlight of strategies on the small-molecule optimization with specific cases, we aim to put forward the importance of structure–thermodynamic relationships (STRs) and structure–kinetic relationships (SKRs), which could provide more guidance to find safe and effective small-molecule drugs.