Kerns Edward H, Di Li
Discovery Analytical Chemistry, Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA.
Drug Discov Today. 2003 Apr 1;8(7):316-23. doi: 10.1016/s1359-6446(03)02649-7.
Drug discovery research organizations are building capability for measuring an ensemble of crucial 'drug-like' properties. These structure-property relationship (SPR) data complement current SAR information. This pharmaceutical profiling strategy enables research teams to better plan and interpret discovery experiments, be alerted to potential 'show stoppers', improve property liabilities, and select the best candidates for advancement. High throughput property assays for physicochemical properties--solubility, permeability, lipophilicity, stability, and pK(a)--in vitro ADME--metabolism, transporters, protein binding and CYP inhibition--and in vivo PK/exposure provide a wealth of data for teams to make informed decisions.
药物研发机构正在建立测量一系列关键“类药”特性的能力。这些结构-性质关系(SPR)数据补充了当前的构效关系(SAR)信息。这种药物分析策略使研究团队能够更好地规划和解释发现实验,警惕潜在的“阻碍因素”,改善性质缺陷,并选择最有前景的候选药物进行推进。针对物理化学性质(溶解度、渗透性、亲脂性、稳定性和pKa)、体外药物代谢动力学(ADME)(代谢、转运体、蛋白结合和CYP抑制)以及体内药代动力学/暴露的高通量性质测定为团队提供了丰富的数据,以便做出明智的决策。