Ligand Detection in the Allosteric World
Ligand Detection in the Allosteric World
复制标题
变构世界中的配体检测
DOI：
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发表时间：
2010
影响因子：
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通讯作者：
T. Kenakin
中科院分区：
文献类型：
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作者：
T. Kenakin
从历史上看，配体的传统筛选已被优化以检测标准的正构激动剂和拮抗剂。然而，随着对细胞功能筛选的日益重视，越来越多的变构配体被发现作为潜在的药物。此外，存在理论原因（增加的选择性、更好地控制生理系统、分别控制亲和力和功效），变构配体可以是优选的治疗化学靶标。这些因素可能使设计高通量筛选以特异性检测功能性变构配体成为可取的。本文讨论了变构配体作为药物的独特功能，以及应考虑的特殊条件，以优化高通量筛选对变构药物的检测。最后，检测对细胞有直接影响的变构配体（无论是传统的激动作用或功能选择性的影响）的可能性进行了讨论，以及在筛选试验中检测这些配体的优化。
Historically, traditional screening for ligands has been optimized to detect standard orthosteric agonists and antagonists. However, with increasing emphasis on cellular functional screens, more allosteric ligands are being discovered as potential drugs. In addition, there are theoretical reasons (increased selectivity, better control of physiological systems, separate control of affinity and efficacy) allosteric ligands may be preferred therapeutic chemical targets. These factors may make it desirable to design high-throughput screens to specifically detect functionally allosteric ligands. This article discusses the unique features of allosteric ligands as drugs as well as the special conditions that should be considered to optimize a high-throughput screen toward the detection of allosteric drugs. Finally, the likelihood of detecting allosteric ligands that have direct effects on cells (either conventional agonism or functionally selective effects) is discussed as well as the optimization of detection of such ligands in screening assays.
代谢型谷氨酸受体 4 (mGluR4) 的新型正变构调节剂 (PAM) 的合成和 SAR。
影响因子：
2.7
作者：
Williams,Richard;Johnson,KariA;Gentry,PatrickR;Niswender,ColleenM;Weaver,CharlesD;Conn,PJeffrey;Lindsley,CraigW;Hopkins,CoreyR
通讯作者：
Hopkins,CoreyR
毒蕈碱受体的正向和负向变构相互作用。
影响因子：
5
作者：
Hejnová,L;Tucek,S;el-Fakahany,EE
通讯作者：
el-Fakahany,EE