Finch Harry
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Drug Discov Today. 2014 Mar;19(3):320-5. doi: 10.1016/j.drudis.2013.10.016. Epub 2013 Oct 31.
Structure-based drug design strategies based on X-ray crystallographic data of ligands bound to biological targets or computationally derived pharmacophore models have been introduced over the past 25 years or so. These have now matured and are deeply embedded in the drug discovery process in most pharmaceutical and biotechnology companies where they continue to play a major part in the discovery of new medicines and drug candidates. Newly developed NMR methods can now provide a full description of the conformations in which ligands exist in free solution, crucially allowing those that are dominant to be identified. Integrating experimentally determined conformational information on active and inactive molecules in drug discovery programmes, alongside the existing techniques, should have a major impact on the success of drug discovery.
在过去25年左右的时间里,基于与生物靶点结合的配体的X射线晶体学数据或计算得出的药效团模型的基于结构的药物设计策略已经被引入。这些策略现在已经成熟,并深深融入了大多数制药和生物技术公司的药物发现过程中,在新药和候选药物的发现中继续发挥着重要作用。新开发的核磁共振方法现在可以全面描述配体在自由溶液中的构象,至关重要的是能够识别出占主导地位的构象。在药物发现计划中,将实验确定的活性和非活性分子的构象信息与现有技术相结合,应该会对药物发现的成功产生重大影响。