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.