Structure-based discovery of β2-adrenergic receptor ligands
Structure-based discovery of β2-adrenergic receptor ligands
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DOI：
10.1073/pnas.0812657106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Shoichet, Brian K.
中科院分区：
文献类型：
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作者：
Kolb, Peter;Rosenbaum, Daniel M.;Shoichet, Brian K.
胺能 G 蛋白偶联受体 (GPCR) 多年来一直是药物研究的主要焦点。部分由于缺乏可靠的受体结构，药物发现工作主要基于配体。最近确定的 β(2)-肾上腺素能受体的 X 射线结构提供了一个机会来研究基于结构的方法固有的优势和局限性，以发现针对该受体和相关 GPCR 靶点的配体。大约 100 万个市售的“类先导”分子与 β(2)-肾上腺素能受体结构对接。在测试 25 个高级分子时，其中 6 个分子具有结合亲和力，具有活性
Aminergic G protein-coupled receptors (GPCRs) have been a major focus of pharmaceutical research for many years. Due partly to the lack of reliable receptor structures, drug discovery efforts have been largely ligand-based. The recently determined X-ray structure of the beta(2)-adrenergic receptor offers an opportunity to investigate the advantages and limitations inherent in a structure-based approach to ligand discovery against this and related GPCR targets. Approximately 1 million commercially available, "lead-like" molecules were docked against the beta(2)-adrenergic receptor structure. On testing of 25 high-ranking molecules, 6 were active with binding affinities