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

• 영문명: Validation and Profiling of Physicochemical Properties Screening Methods for New Drug Candidate Optimization in Early Drug discovery
• 발행기관: 대한약학회
• 저자명: 이진석(Jinseok Lee) 안성훈(Sung-Hoon Ahn)
• 간행물 정보: 『약학회지』제62권 제4호(2018년), 274~283쪽, 전체 10쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2018.08.30

영문 초록

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.

목차

서 론 (Introduction)

실험 방법 (Experimental Methods)

결과 및 고찰 (Results and Discussion)

결 론 (Conclusion)

키워드

Physicochemical property ionization constant lipophilicity solubility in silico prediction pharmacokinetics drug discovery