Durham Timothy B, Blanco Maria-Jesus
Discovery Chemistry Research and Technologies, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Bioorg Med Chem Lett. 2015 Mar 1;25(5):998-1008. doi: 10.1016/j.bmcl.2014.12.076. Epub 2015 Jan 12.
The pharmaceutical industry is currently facing multiple challenges, in particular the low number of new drug approvals in spite of the high level of R&D investment. In order to improve target selection and assess properly the clinical hypothesis, it is important to start building an integrated drug discovery approach during Lead Generation. This should include special emphasis on evaluating target engagement in the target tissue and linking preclinical to clinical readouts. In this review, we would like to illustrate several strategies and technologies for assessing target engagement and the value of its application to medicinal chemistry efforts.
制药行业目前正面临多重挑战，尤其是尽管研发投入水平很高，但新药获批数量却很低。为了改进靶点选择并正确评估临床假设，在先导化合物发现阶段开始构建综合药物发现方法非常重要。这应特别强调评估靶点在靶组织中的参与情况，并将临床前数据与临床结果联系起来。在本综述中，我们将阐述几种评估靶点参与情况的策略和技术及其在药物化学研究中的应用价值。
