Department of Quantitative and Computational Biology, Bridge Institute, USC Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA.
Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Biosciences, University of Southern California, Los Angeles, CA, USA.
Handb Exp Pharmacol. 2022;271:41-64. doi: 10.1007/164_2021_461.
The structure of the human kappa opioid receptor (KOR) in complex with the long-acting antagonist JDTic was solved crystallographically in 2012 and, along with structures of other opioid receptors, revolutionized our understanding of opioid system function and pharmacology. More recently, active state KOR structure was also determined, giving important insights into activation mechanisms of the receptor. In this review, we will discuss how the understanding of atomistic structures of KOR established a key platform for deciphering details of subtype and functional selectivity of KOR-targeting ligands and for discovery of new chemical probes with potentially beneficial pharmacological profiles.
2012 年，人类 κ 阿片受体（KOR）与长效拮抗剂 JDTic 的复合物结构通过晶体学方法得以解决，这与其他阿片受体的结构一起，彻底改变了我们对阿片系统功能和药理学的理解。最近，也确定了活性状态 KOR 的结构，为受体的激活机制提供了重要的见解。在这篇综述中，我们将讨论 KOR 的原子结构的理解如何为破译 KOR 靶向配体的亚型和功能选择性的细节以及发现具有潜在有益的药理学特性的新化学探针奠定了关键平台。
