High Throughput Screening Laboratory, Institute for Advancing Medical Innovations, University of Kansas, Lawrence, KS 66047, USA.
Curr Pharm Biotechnol. 2010 Nov;11(7):764-78. doi: 10.2174/138920110792927757.
High throughput screening (HTS) facilitates screening large numbers of compounds against a biochemical target of interest using validated biological or biophysical assays. In recent years, a significant number of drugs in clinical trails originated from HTS campaigns, validating HTS as a bona fide mechanism for hit finding. In the current drug discovery landscape, the pharmaceutical industry is embracing open innovation strategies with academia to maximize their research capabilities and to feed their drug discovery pipeline. The goals of academic research have therefore expanded from target identification and validation to probe discovery, chemical genomics, and compound library screening. This trend is reflected in the emergence of HTS centers in the public domain over the past decade, ranging in size from modestly equipped academic screening centers to well endowed Molecular Libraries Probe Centers Network (MLPCN) centers funded by the NIH Roadmap initiative. These centers facilitate a comprehensive approach to probe discovery in academia and utilize both classical and cutting-edge assay technologies for executing primary and secondary screening campaigns. The various facets of academic HTS centers as well as their implications on technology transfer and drug discovery are discussed, and a roadmap for successful drug discovery in the public domain is presented. New lead discovery against therapeutic targets, especially those involving the rare and neglected diseases, is indeed a Mount Everestonian size task, and requires diligent implementation of pharmaceutical industry's best practices for a successful outcome.
高通量筛选 (HTS) 通过验证的生物或物理生物测定法,促进了针对感兴趣的生化靶标对大量化合物进行筛选。近年来,大量处于临床试验阶段的药物源自 HTS 活动,这验证了 HTS 是一种可靠的发现命中的机制。在当前的药物发现格局中,制药行业正在与学术界一起采用开放式创新策略,以最大化其研究能力并为其药物发现管道提供支持。因此,学术研究的目标已从靶标鉴定和验证扩展到探针发现、化学基因组学和化合物库筛选。这种趋势反映在过去十年中公共领域中 HTS 中心的出现,这些中心的规模从装备适度的学术筛选中心到由 NIH 路线图计划资助的资源充足的分子库探针中心网络 (MLPCN) 中心不等。这些中心促进了学术界中探针发现的全面方法,并利用经典和前沿的测定技术来执行初级和二级筛选活动。本文讨论了学术 HTS 中心的各个方面及其对技术转让和药物发现的影响,并提出了在公共领域中成功进行药物发现的路线图。针对治疗靶标的新先导化合物发现,特别是那些涉及罕见和被忽视疾病的靶标,确实是一项艰巨的任务,需要认真实施制药行业的最佳实践,才能取得成功。