Coussens Nathan P, Braisted John C, Peryea Tyler, Sittampalam G Sitta, Simeonov Anton, Hall Matthew D
National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland.
National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
Pharmacol Rev. 2017 Oct;69(4):479-496. doi: 10.1124/pr.117.013755.
High-throughput screening (HTS) of small-molecule libraries accelerates the discovery of chemical leads to serve as starting points for probe or therapeutic development. With this approach, thousands of unique small molecules, representing a diverse chemical space, can be rapidly evaluated by biologically and physiologically relevant assays. The origins of numerous United States Food and Drug Administration-approved cancer drugs are linked to HTS, which emphasizes the value in this methodology. The National Institutes of Health Molecular Libraries Program made HTS accessible to the public sector, enabling the development of chemical probes and drug-repurposing initiatives. In this work, the impact of HTS in the field of oncology is considered among both private and public sectors. Examples are given for the discovery and development of approved cancer drugs. The importance of target validation is discussed, and common assay approaches for screening are reviewed. A rigorous examination of the PubChem database demonstrates that public screening centers are contributing to early-stage drug discovery in oncology by focusing on new targets and developing chemical probes. Several case studies highlight the value of different screening strategies and the potential for drug repurposing.
小分子文库的高通量筛选（HTS）加速了化学先导物的发现，这些先导物可作为探针或治疗药物开发的起点。通过这种方法，可以通过生物学和生理学相关检测快速评估数千种代表不同化学空间的独特小分子。许多美国食品药品监督管理局批准的抗癌药物都起源于高通量筛选，这凸显了该方法的价值。美国国立卫生研究院分子文库计划使公共部门能够使用高通量筛选，推动了化学探针的开发和药物重新利用计划。在这项工作中，我们将探讨高通量筛选在肿瘤学领域对私营和公共部门的影响。文中给出了已批准抗癌药物发现和开发的实例。讨论了靶点验证的重要性，并回顾了常见的筛选检测方法。对PubChem数据库的严格审查表明，公共筛选中心通过专注于新靶点和开发化学探针，正在为肿瘤学的早期药物发现做出贡献。几个案例研究突出了不同筛选策略的价值以及药物重新利用的潜力。
