Kenakin Terry
GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA.
Nat Rev Drug Discov. 2005 Nov;4(11):919-27. doi: 10.1038/nrd1875.
New perspectives on the complexity of G-protein-coupled receptor (GPCR) signalling and the increased resolution of existing tools for studying GPCR behaviour has led to the conception of new hypotheses that affect the discovery of drugs acting at GPCRs. Taking into consideration the novel concepts of collateral efficacy and permissive antagonism in the search for synthetic agonists and antagonists, respectively, will be essential in the search for drugs with unique therapeutic profiles. Here, the design of drugs against HIV is used as an example of how these concepts might be taken into consideration for GPCR-targeted drugs in general.
对G蛋白偶联受体（GPCR）信号传导复杂性的新观点以及用于研究GPCR行为的现有工具分辨率的提高，催生了影响作用于GPCR的药物发现的新假说。在寻找合成激动剂和拮抗剂的过程中，分别考虑旁系效应和允许性拮抗作用的新概念，对于寻找具有独特治疗特性的药物至关重要。在此，以抗HIV药物的设计为例，说明一般情况下针对GPCR的药物如何考虑这些概念。
