ArticleeLife2021
Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site.
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Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46citing papers in PubMed
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46 citing papers in PubMed, 65 citations in OpenAlex.
- Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.Journal of chemical information and modeling · 2026Article
- Mechanistic insights into ligand selectivity inActa pharmaceutica Sinica. B · 2026Article
- Mechanistic Insights into G Protein-Biased κ-Opioid Receptor Signaling Using Dual-Charged Naltrexamine Amides.Journal of medicinal chemistry · 2026Article
- Synthesis and Pharmacology of a Morphinan-Derived Dual Mu-Kappa Opioid Receptor Agonist Analgesic.ACS chemical neuroscience · 2025Article
- Total synthesis and biological activity of "carbamorphine": O-to-CHProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Docking 14 Million Virtual Isoquinuclidines against the μ and κ Opioid Receptors Reveals Dual Antagonists-Inverse Agonists with Reduced Withdrawal Effects.ACS central science · 2025Article
- Structural Determinants of Buprenorphine Partial Agonism at the μ-Opioid Receptor.Journal of chemical information and modeling · 2025Article
- Morphine-Induced Antinociception Is Potentiated and Dopamine Elevations Are Inhibited by the Biased Kappa Opioid Receptor Agonist Triazole 1.1.ACS chemical neuroscience · 2025Article
- Article
- Structure-guided design of partial agonists at an opioid receptor.Nature communications · 2025Article
- Docking 14 million virtual isoquinuclidines against the mu and kappa opioid receptors reveals dual antagonists-inverse agonists with reduced withdrawal effects.bioRxiv : the preprint server for biology · 2025Article
- Opioid system and related ligands: from the past to future perspectives.Journal of anesthesia, analgesia and critical care · 2024Review
- Biased Signaling Agonists Promote Distinct Phosphorylation and Conformational States of the Dopamine D3 Receptor.International journal of molecular sciences · 2024Article
- Signaling Modulation Mediated by Ligand Water Interactions with the Sodium Site at μOR.ACS central science · 2024Article
- Structure-Guided Design of Partial Agonists at an Opioid Receptor.Research square · 2024Article
- Article
- Peptide-derived ligands for the discovery of safer opioid analgesics.Drug discovery today · 2024Review
- Structural insights into the unexpected agonism of tetracyclic antidepressants at serotonin receptors 5-HTScience advances · 2024Article
- Design and structural validation of peptide-drug conjugate ligands of the kappa-opioid receptor.Nature communications · 2023Article
- IUPHAR themed review: Opioid efficacy, bias, and selectivity.Pharmacological research · 2023Review
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Authors and funding
24 authors at 7 institutions in 1 country.
Rajendra Uprety *Department of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.
Tao Che *Department of Pharmacology, University of North Carolina, Chapel Hill, United States.
Saheem A Zaidi *Department of Quantitative and Computational Biology, Department of Chemistry, Bridge Institute, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, United States.ORCID 0000-0001-7531-3587
Steven G GrinnellDivision of Molecular Therapeutics, New York State Psychiatric Institute and Departments of Psychiatry, Pharmacology, Columbia University Vagelos College of Physicians & Surgeons, New York, United States.
Balázs R VargaCenter for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University School of Medicine, St. Louis, United States.ORCID 0000-0003-0986-9477
Abdelfattah FaouziCenter for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University School of Medicine, St. Louis, United States.ORCID 0000-0002-9059-4791
Samuel T SlocumDepartment of Pharmacology, University of North Carolina, Chapel Hill, United States.
Abdullah AllaoaDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.
András VaradiDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.ORCID 0000-0001-5591-377X
Melissa NelsonDivision of Molecular Therapeutics, New York State Psychiatric Institute and Departments of Psychiatry, Pharmacology, Columbia University Vagelos College of Physicians & Surgeons, New York, United States.
Sarah M BernhardCenter for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University School of Medicine, St. Louis, United States.ORCID 0000-0001-8549-0413
Elizaveta KulkoDivision of Molecular Therapeutics, New York State Psychiatric Institute and Departments of Psychiatry, Pharmacology, Columbia University Vagelos College of Physicians & Surgeons, New York, United States.
Valerie Le RouzicDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.
Shainnel O EansDepartment of Pharmacodynamics, University of Florida, Gainesville, United States.
Chloe A SimonsDepartment of Pharmacodynamics, University of Florida, Gainesville, United States.
Amanda HunkeleDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.
Joan SubrathDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.
Ying Xian PanDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.
Jonathan A JavitchDivision of Molecular Therapeutics, New York State Psychiatric Institute and Departments of Psychiatry, Pharmacology, Columbia University Vagelos College of Physicians & Surgeons, New York, United States.ORCID 0000-0001-7395-2967
Jay P McLaughlinDepartment of Pharmacodynamics, University of Florida, Gainesville, United States.
Bryan L RothDepartment of Pharmacology, University of North Carolina, Chapel Hill, United States.
Gavril W PasternakDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.
Vsevolod KatritchDepartment of Quantitative and Computational Biology, Department of Chemistry, Bridge Institute, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, United States.ORCID 0000-0003-3883-4505
Susruta MajumdarDepartment of Neurology and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, United States.ORCID 0000-0002-2931-3823
Memorial Sloan Kettering Cancer Center · USColumbia University · USUniversity of Florida · USUniversity of Health Sciences and Pharmacy · USUniversity of North Carolina at Chapel Hill · USUniversity of Southern California · USRutgers, The State University of New Jersey · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MStructure of the Dopamine D2-Like Receptor Binding SitesR01MH054137 · NIMH · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI JAVITCH, JONATHAN A · 1995 to 2025
$12.0MTraining in Schizophrenia and Psychotic Disorders: From Animal Models to PatientsT32MH018870 · NIMH · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Guillermo Horga, Christoph Kellendonk · 1988 to 2026
$9.8MTRAINING IN BEHAV. PHARMACOLOGY OF HUMAN DRUG DEPENDENCET32DA007242 · NIDA · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI HEIL, SARAH H, HIGGINS, STEPHEN T · 1990 to 2025
$8.2MStructure-Function of Opioid ReceptorsP01DA035764 · NIDA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROTH, BRYAN L., STEVENS, RAYMOND C · 2014 to 2018
$7.1MSynthesis &Pharmacology of Novel Opiates and SystemsR01DA006241 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 1990 to 2018
$6.4MMolecular Details of Psychoactive Drug ActionsR01MH112205 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Bryan L. Roth, Brian K Shoichet · 2017 to 2026
$6.1MPHARMACOLOGY OF OPIOID RECEPTOR SUBTYPESR01DA007242 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 1991 to 2022
$6.0MMechanistic insights into LSD actions at 5-HT2A serotonin receptorsR37DA045657 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Bryan L. Roth · 2018 to 2026
$5.8MChemistry and Biology of Mitragynine AlkaloidsR01DA046487 · NIDA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI MAJUMDAR, SUSRUTA, SAMES, DALIBOR · 2018 to 2022
$3.0MAlternative pre-mRNA splicing of mu opioid receptor gene and mu opioid actionsR01DA042888 · NIDA · SLOAN-KETTERING INST CAN RESEARCH · PI PAN, YING-XIAN · 2017 to 2021
$1.9MPHARMACOLOGY OF OPIOID RECEPTOR SUBTYPESR37DA007242 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PASTERNAK, GAVRIL W · 1996 to 2004
$1.5MNCI NIH HHS P30 CA008748NIAAA NIH HHS R21 AA026949NIDA NIH HHS P01 DA035764NIDA NIH HHS R01 DA006241NIDA NIH HHS R01 DA007242NIDA NIH HHS R01 DA042888NIDA NIH HHS R01 DA046487NIDA NIH HHS R21 DA038858NIDA NIH HHS R21 DA045884NIDA NIH HHS R21 DA046714NIDA NIH HHS R33 DA038858NIDA NIH HHS R33 DA045884NIDA NIH HHS R37 DA007242NIDA NIH HHS R37 DA045657NIDA NIH HHS T32 DA007242NIH HHS W81XWH-17-1-0256NIMH NIH HHS R01 MH054137NIMH NIH HHS R01 MH112205NIMH NIH HHS T32 MH018870
Abstract
Controlling receptor functional selectivity profiles for opioid receptors is a promising approach for discovering safer analgesics; however, the structural determinants conferring functional selectivity are not well understood. Here, we used crystal structures of opioid receptors, including the recently solved active state kappa opioid complex with
Indexed as
Amino Acid MotifsAnalgesicsAnimalsBinding SitesLigandsMaleMiceMice, Inbred C57BLMolecular Docking SimulationMorphinansReceptors, Opioid, kappaReceptors, Opioid, muStructure-Activity Relationship17-cyclopropylmethyl-3-hydroxy-4,5-epoxy-7,8-en-6-((3'-iodo)benzamido)morphinanAnalgesicsLigandsMorphinansReceptors, Opioid, kappaReceptors, Opioid, mubiochemistryboat/chairchemical biologyfunctional selectivityGPCR biasmousesafer opioidsstructure-based drug design
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