Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development

Li, Zoe; Huang, Ruili; Xia, Menghang; Chang, Nancy; Guo, Wenjing; Liu, Jie; Dong, Fan; Liu, Bailang; Varghese, Ann; Aslam, Aasma; Patterson, Tucker A.; Hong, Huixiao

doi:10.3390/molecules29112635

Decoding the κ Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development

Journal Article · Mon Jun 03 00:00:00 EDT 2024 · Molecules

DOI:https://doi.org/10.3390/molecules29112635· OSTI ID:2471342

Li, Zoe ^[1]; Huang, Ruili ^[2]; Xia, Menghang ^[2]; Chang, Nancy ^[3]; Guo, Wenjing ^[1]; Liu, Jie ^[1]; Dong, Fan ^[1]; Liu, Bailang ^[1]; Varghese, Ann ^[1]; Aslam, Aasma ^[1]; Patterson, Tucker A. ^[1]; ^[2]

US Food and Drug Administration (USFDA), Jefferson, AR (United States)
National Institutes of Health (NIH), Bethesda, MD (United States)
US Food and Drug Administration (USFDA), Silver Spring, MD (United States)

The opioid crisis in the United States is a significant public health issue, with a nearly threefold increase in opioid-related fatalities between 1999 and 2014. In response to this crisis, society has made numerous efforts to mitigate its impact. Recent advancements in understanding the structural intricacies of the κ opioid receptor (KOR) have improved our knowledge of how opioids interact with their receptors, triggering downstream signaling pathways that lead to pain relief. This review concentrates on the KOR, offering crucial structural insights into the binding mechanisms of both agonists and antagonists to the receptor. Through comparative analysis of the atomic details of the binding site, distinct interactions specific to agonists and antagonists have been identified. These insights not only enhance our understanding of ligand binding mechanisms but also shed light on potential pathways for developing new opioid analgesics with an improved risk-benefit profile.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2471342

Journal Information:: Molecules, Journal Name: Molecules Journal Issue: 11 Vol. 29; ISSN 1420-3049

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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