초기 신약개발 단계에서의 신약후보물질 최적화를 위한 물성 스크리닝 방법 검증 및 프로파일링

초록

Drug-like properties based on physicochemical properties are important to confer good ADME/PK characteristicsfor sufficiently effective efficacy and safety on preclinical and clinical trials. Therefore, accurate estimation andoptimization of physicochemical properties such as ionization constant, lipophilicity, permeability, and solubility are importantfactors for pharmacokinetic properties including clearance, half-life, bioavailability, drug-drug interactions. This studywas performed to validate screening method of physicochemical properties. The commercially available drugs were usedto validate analytical method system of physicochemical properties and experimental values were compared with literaturevalues and in silico predictions. The experimental pKa values were in very good accordance with literature values in bothcase of pKa PRO (r2= 0.82) and GLpKa (r2= 0.87). Experimental values and in silico predictions of lipophilicity were alsoin very good accordance with literature values (r2 > 0.82). Experimental physicochemical values of KR-62980 as a new drugcandidate showed similar values to in silico predictions. Finally, screenings of physicochemical properties can be applied welland this result may cause lowering cost and accelerating screening speed for the integration of ADME/PK screening datain early stage of new drug discovery.

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