Dahlin Jayme L, Walters Michael A
Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Future Med Chem. 2014 Jul;6(11):1265-90. doi: 10.4155/fmc.14.60.
It is increasingly clear that academic high-throughput screening (HTS) and virtual HTS triage suffers from a lack of scientists trained in the art and science of early drug discovery chemistry. Many recent publications report the discovery of compounds by screening that are most likely artifacts or promiscuous bioactive compounds, and these results are not placed into the context of previous studies. For HTS to be most successful, it is our contention that there must exist an early partnership between biologists and medicinal chemists. Their combined skill sets are necessary to design robust assays and efficient workflows that will weed out assay artifacts, false positives, promiscuous bioactive compounds and intractable screening hits, efforts that ultimately give projects a better chance at identifying truly useful chemical matter. Expertise in medicinal chemistry, cheminformatics and purification sciences (analytical chemistry) can enhance the post-HTS triage process by quickly removing these problematic chemotypes from consideration, while simultaneously prioritizing the more promising chemical matter for follow-up testing. It is only when biologists and chemists collaborate effectively that HTS can manifest its full promise.
越来越明显的是，学术性高通量筛选（HTS）和虚拟HTS筛选存在一个问题，即缺乏接受过早期药物发现化学技术与科学培训的科学家。最近许多出版物报道通过筛选发现的化合物很可能是假象或混杂的生物活性化合物，而且这些结果并未与先前的研究相结合。为了使HTS取得最大成功，我们认为生物学家和药物化学家之间必须尽早建立合作关系。他们的综合技能对于设计强大的检测方法和高效的工作流程至关重要，这些方法和流程能够排除检测假象、假阳性、混杂的生物活性化合物以及难以处理的筛选命中物，这些努力最终会使项目更有可能识别出真正有用的化学物质。药物化学、化学信息学和纯化科学（分析化学）方面的专业知识可以通过迅速排除这些有问题的化学类型来加强HTS后的筛选过程，同时优先考虑更有前景的化学物质进行后续测试。只有当生物学家和化学家有效合作时，HTS才能充分发挥其潜力。
