Typically, in the Lead Finding (LF) stage, compounds' solubility,
lipophilicity, permeability, and microsomal stability are determined
first. The obtained data are used to build the structure-property
relationship of compounds, screen chemical structure categories, and
confirm the priority of multiple structural backbones. At the Lead
Optimization (LO) and Pre-Clinical Candidate (PCC) stages, comprehensive in vitro ADME
studies are usually required. These include multi-species metabolic
stability, plasma protein binding, transporters-related drug
interaction, and inhibition of the drug-metabolizing enzymes combined
with animal PK data to predict human PK performance. In the
Investigational New Drug (IND) stage, a comprehensive evaluation of in vitro ADME properties is required and conducted per the requirements of drug registration authorities. It should be noted that the in vitro ADME screening study is usually not designed for regulatory submission purpose.