Ray Peter C, Kiczun Michael, Huggett Margaret, Lim Andrew, Prati Federica, Gilbert Ian H, Wyatt Paul G
Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.
Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.
Drug Discov Today. 2017 Jan;22(1):43-56. doi: 10.1016/j.drudis.2016.10.005. Epub 2016 Oct 26.
The availability of suitable diverse fragment- and lead-oriented screening compounds is key for the identification of suitable chemical starting points for drug discovery programs. The physicochemical properties of molecules are crucial in determining the success of small molecules in clinical development, yet reports suggest that pharmaceutical and academic sectors often produce molecules with poor drug-like properties. We present a platform to design novel, high quality and diverse fragment- and lead-oriented libraries with appropriate physicochemical properties in a cost-efficient manner. This approach has the potential to assist the way libraries are constructed by significantly addressing the historical uneven exploration of chemical space for drug discovery. Additionally, this platform can teach undergraduates and graduates about compound library design.
获得合适的、多样化的面向片段和先导物的筛选化合物，是为药物发现项目确定合适化学起始点的关键。分子的物理化学性质对于小分子在临床开发中的成功起着至关重要的作用，但报告表明，制药和学术领域常常产出具有不良类药性质的分子。我们提出了一个平台，以经济高效的方式设计具有适当物理化学性质的新型、高质量且多样化的面向片段和先导物的文库。这种方法有可能显著解决药物发现中化学空间探索历史上的不均衡问题，从而有助于文库的构建方式。此外，该平台可以向本科生和研究生传授化合物文库设计知识。
