Validation and Profiling of Physicochemical Properties Screening Methods for New Drug Candidate Optimization in Early Drug discovery

Abstract

Drug-like properties based on physicochemical properties are important to confer good ADME/PK char-acteristics for sufficiently effective efficacy and safety on preclinical and clinical trials. Therefore, accurate estimation and optimization of physicochemical properties such as ionization constant, lipophilicity, permeability, and solubility are import-ant factors for pharmacokinetic properties including clearance, half-life, bioavailability, drug-drug interactions. This study was performed to validate screening method of physicochemical properties. The commercially available drugs were used to validate analytical method system of physicochemical properties and experimental values were compared with literature values and in silico predictions. The experimental pKa values were in very good accordance with literature values in both case of pKa PRO (r² = 0.82) and GLpKa (r² = 0.87). Experimental values and in silico predictions of lipophilicity were also in very good accordance with literature values (r² > 0.82). Experimental physicochemical values of KR-62980 as a new drug candidate showed similar values to in silico predictions. Finally, screenings of physicochemical properties can be applied well and this result may cause lowering cost and accelerating screening speed for the integration of ADME/PK screening data in early stage of new drug discovery.