ADMET In Vitro Profiling: Utility and Applications in Lead Discovery

ADMET properties are a vital integral part of drug discovery because they determine the pharmacokinetics and safety of clinical development candidates. Diverse ADMET profiling assays have been developed and implemented to provide property data for drug discovery team decision making. Their utility and applications in lead discovery include the following: lead selection, diagnosis of poor PK, guidance for structure modification, solving specific project team property issues, providing accurate biological data for SAR, selecting compounds for in vivo PK and PD studies, and improving dosing for optimum exposure in vivo. ADMET properties are discussed along with case studies and assays. Keywords: absorption; ADMET; assays; blood–brain barrier; bioassay; Caco-2; cytochrome P450 (CYP); distribution; drug–drug interaction; drug-like properties; excretion; hERG blocking; in vitro assay; lipophilicity; metabolism; optimization; PAMPA; permeability; pharmacokinetics; physicochemical; pKa; protein binding; rule of five; stability; solubility; toxicity; transporters