ArticleMolecular pharmacology2015
Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Nociceptin/orphanin FQ receptor ligands and translational challenges: focus on cebranopadol as an innovative analgesic.British journal of anaesthesia · 2018Pooled it
- Recommended Opioid Receptor Tool Compounds: ComparativeACS pharmacology & translational science · 2025Article
- Detecting and measuring of GPCR signaling - comparison of human induced pluripotent stem cells and immortal cell lines.Frontiers in endocrinology · 2023Review
- Differential In Vitro Pharmacological Profiles of Structurally Diverse Nociceptin Receptor Agonists in Activating G Protein and Beta-Arrestin Signaling at the Human Nociceptin Opioid Receptor.Molecular pharmacology · 2021Article
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Functional Selectivity Does Not Predict Antinociceptive/Locomotor Impairing Potencies of NOP Receptor Agonists.Frontiers in neuroscience · 2021Article
- Biased Agonism at Nociceptin/Orphanin FQ Receptors: A Structure Activity Study on N/OFQ(1-13)-NHJournal of medicinal chemistry · 2020Article
- Biased Opioid Ligands.Molecules (Basel, Switzerland) · 2020Review
- Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists.Science signaling · 2019Article
- Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity.The international journal of neuropsychopharmacology · 2018Review
- Article
- In vitro pharmacological characterization of a novel unbiased NOP receptor-selective nonpeptide agonist AT-403.Pharmacology research & perspectives · 2017Article
- In vitro functional characterization of novel nociceptin/orphanin FQ receptor agonists in recombinant and native preparations.European journal of pharmacology · 2016Article
- Pharmacological characterization of cebranopadol a novel analgesic acting as mixed nociceptin/orphanin FQ and opioid receptor agonist.Pharmacology research & perspectives · 2016Article
- Beta-arrestin 2 rather than G protein efficacy determines the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands.Neuropharmacology · 2016Article
- A Novel, Orally Bioavailable Nociceptin Receptor Antagonist, LY2940094, Reduces Ethanol Self-Administration and Ethanol Seeking in Animal Models.Alcoholism, clinical and experimental research · 2016Article
- Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems.Pharmacological reviews · 2016Review
- Novel Synthesis and Pharmacological Characterization of NOP Receptor Agonist 8-[(1S,3aS)-2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro 64-6198).ACS chemical neuroscience · 2015Article
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Authors and funding
7 authors.
Funding
Abstract
Comprehensive studies that consolidate selective ligands, quantitative comparisons of G protein versus arrestin-2/3 coupling, together with structure-activity relationship models for G protein-coupled receptor (GPCR) systems are less commonly employed. Here we examine biased signaling at the nociceptin/orphanin FQ opioid receptor (NOPR), the most recently identified member of the opioid receptor family. Using real-time, live-cell assays, we identified the signaling profiles of several NOPR-selective ligands in upstream GPCR signaling (G protein and arrestin pathways) to determine their relative transduction coefficients and signaling bias. Complementing this analysis, we designed novel ligands on the basis of NOPR antagonist J-113,397 [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] to explore structure-activity relationships. Our study shows that NOPR is capable of biased signaling, and further, the NOPR selective ligands MCOPPB [1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-(3R)-3-piperidinyl-1H-benzimidazole trihydrochloride] and NNC 63-0532 [8-(1-naphthalenylmethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-3-acetic acid, methyl ester] are G protein-biased agonists. Additionally, minor structural modification of J-113,397 can dramatically shift signaling from antagonist to partial agonist activity. We explore these findings with in silico modeling of binding poses. This work is the first to demonstrate functional selectivity and identification of biased ligands at the nociceptin opioid receptor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.