{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:43:53Z","timestamp":1789983833397,"version":"4.0.1"},"reference-count":49,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2014,1]]},"DOI":"10.1124\/mol.113.089649","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T14:59:41Z","timestamp":1381503581000},"page":"83-90","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":120,"title":["Identification of Novel Functionally Selective \u03ba-Opioid Receptor Scaffolds"],"prefix":"10.1016","volume":"85","author":[{"given":"Kate L.","family":"White","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex P.","family":"Scopton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Laure","family":"Rives","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan V.","family":"Bikbulatov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakar R.","family":"Polepally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrance","family":"Kenakin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Javitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan K.","family":"Zjawiony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan L.","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/mol.113.089649_bib1","doi-asserted-by":"crossref","first-page":"18488","DOI":"10.1073\/pnas.1104807108","article-title":"Discovery of \u03b2-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy","volume":"108","author":"Allen","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.113.089649_bib2","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1046\/j.1471-4159.1997.69062405.x","article-title":"Agonist-induced phosphorylation of the kappa-opioid receptor","volume":"69","author":"Appleyard","year":"1997","journal-title":"J Neurochem"},{"key":"10.1124\/mol.113.089649_bib3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1073\/pnas.0710487105","article-title":"The genetic design of signaling cascades to record receptor activation","volume":"105","author":"Barnea","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.113.089649_bib4","doi-asserted-by":"crossref","first-page":"8269","DOI":"10.1074\/jbc.M006968200","article-title":"The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis","volume":"276","author":"Bhatnagar","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.113.089649_bib5","first-page":"141","article-title":"Operational models of pharmacological agonism","volume":"220","author":"Black","year":"1983","journal-title":"Proc R Soc Lond"},{"key":"10.1124\/mol.113.089649_bib6","doi-asserted-by":"crossref","first-page":"18081","DOI":"10.1074\/jbc.M513640200","article-title":"Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes","volume":"281","author":"Bruchas","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.113.089649_bib7","doi-asserted-by":"crossref","first-page":"11614","DOI":"10.1523\/JNEUROSCI.3769-07.2007","article-title":"Stress-induced p38 mitogen-activated protein kinase activation mediates kappa-opioid-dependent dysphoria","volume":"27","author":"Bruchas","year":"2007","journal-title":"J Neurosci"},{"key":"10.1124\/mol.113.089649_bib8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00213-010-1806-y","article-title":"Kinase cascades and ligand-directed signaling at the kappa opioid receptor","volume":"210","author":"Bruchas","year":"2010","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1124\/mol.113.089649_bib9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.pharmthera.2009.05.008","article-title":"Kappa-opioid ligands in the study and treatment of mood disorders","volume":"123","author":"Carlezon","year":"2009","journal-title":"Pharmacol Ther"},{"key":"10.1124\/mol.113.089649_bib10","doi-asserted-by":"crossref","first-page":"7141","DOI":"10.1021\/jm300603y","article-title":"Structure-functional selectivity relationship studies of \u03b2-arrestin-biased dopamine D\u2082 receptor agonists","volume":"55","author":"Chen","year":"2012","journal-title":"J Med Chem"},{"key":"10.1124\/mol.113.089649_bib11","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1527-3458.2005.tb00270.x","article-title":"Bremazocine: a kappa-opioid agonist with potent analgesic and other pharmacologic properties","volume":"11","author":"Dortch-Carnes","year":"2005","journal-title":"CNS Drug Rev"},{"key":"10.1124\/mol.113.089649_bib12","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1124\/mol.63.5.961","article-title":"The interaction of a constitutively active arrestin with the arrestin-insensitive 5-HT(2A) receptor induces agonist-independent internalization","volume":"63","author":"Gray","year":"2003","journal-title":"Mol Pharmacol"},{"key":"10.1124\/mol.113.089649_bib13","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1124\/mol.109.058057","article-title":"Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment","volume":"76","author":"Huang","year":"2009","journal-title":"Mol Pharmacol"},{"key":"10.1124\/mol.113.089649_bib14","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature10726","article-title":"Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons","volume":"481","author":"Huang","year":"2011","journal-title":"Nature"},{"key":"10.1124\/mol.113.089649_bib15","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"ZINC\u2014a free database of commercially available compounds for virtual screening","volume":"45","author":"Irwin","year":"2005","journal-title":"J Chem Inf Model"},{"key":"10.1124\/mol.113.089649_bib16","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1021\/ci3001277","article-title":"ZINC: A free tool to discover chemistry for biology","volume":"52","author":"Irwin","year":"2012","journal-title":"J Chem Inf Model"},{"key":"10.1124\/mol.113.089649_bib17","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S0165-6147(00)89032-X","article-title":"Agonist-receptor efficacy. II. Agonist trafficking of receptor signals","volume":"16","author":"Kenakin","year":"1995","journal-title":"Trends Pharmacol Sci"},{"key":"10.1124\/mol.113.089649_bib18","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1021\/cn200111m","article-title":"A simple method for quantifying functional selectivity and agonist bias","volume":"3","author":"Kenakin","year":"2012","journal-title":"ACS Chem Neurosci"},{"key":"10.1124\/mol.113.089649_bib19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrd3954","article-title":"Signalling bias in new drug discovery: detection, quantification and therapeutic impact","volume":"12","author":"Kenakin","year":"2013","journal-title":"Nat Rev Drug Discov"},{"key":"10.1124\/mol.113.089649_bib20","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.brainres.2009.09.074","article-title":"Dynorphin, stress, and depression","volume":"1314","author":"Knoll","year":"2010","journal-title":"Brain Res"},{"key":"10.1124\/mol.113.089649_bib21","first-page":"1078","article-title":"In vitro studies on metabolism of salvinorin A. Pharm","volume":"47","author":"Kutrzeba","year":"2009","journal-title":"Biol."},{"key":"10.1124\/mol.113.089649_bib22","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1523\/JNEUROSCI.4458-07.2008","article-title":"The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system","volume":"28","author":"Land","year":"2008","journal-title":"J Neurosci"},{"key":"10.1124\/mol.113.089649_bib23","doi-asserted-by":"crossref","first-page":"19168","DOI":"10.1073\/pnas.0910705106","article-title":"Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking","volume":"106","author":"Land","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.113.089649_bib24","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1126\/science.1215802","article-title":"Biased signaling pathways in \u03b22-adrenergic receptor characterized by 19F-NMR","volume":"335","author":"Liu","year":"2012","journal-title":"Science"},{"key":"10.1124\/mol.113.089649_bib25","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0165-6147(90)90321-X","article-title":"Kappa-opioid receptors and analgesia","volume":"11","author":"Millan","year":"1990","journal-title":"Trends Pharmacol Sci"},{"key":"10.1124\/mol.113.089649_bib26","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.cell.2013.01.008","article-title":"The dynamic process of \u03b2(2)-adrenergic receptor activation","volume":"152","author":"Nygaard","year":"2013","journal-title":"Cell"},{"key":"10.1124\/mol.113.089649_bib27","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1126\/science.3016896","article-title":"Psychotomimesis mediated by kappa opiate receptors","volume":"233","author":"Pfeiffer","year":"1986","journal-title":"Science"},{"key":"10.1124\/mol.113.089649_bib28","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1039\/c1md00192b","article-title":"Potential drug abuse therapeutics derived from the hallucinogenic natural product salvinorin A","volume":"2","author":"Prevatt-Smith","year":"2011","journal-title":"Medchemcomm"},{"key":"10.1124\/mol.113.089649_bib29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0969-8051(01)00285-2","article-title":"[(11)C]-GR89696, a potent kappa opiate receptor radioligand; in vivo binding of the R and S enantiomers","volume":"29","author":"Ravert","year":"2002","journal-title":"Nucl Med Biol"},{"key":"10.1124\/mol.113.089649_bib30","doi-asserted-by":"crossref","first-page":"27050","DOI":"10.1074\/jbc.C112.387332","article-title":"6\u2032-Guanidinonaltrindole (6\u2032-GNTI) is a G protein-biased \u03ba-opioid receptor agonist that inhibits arrestin recruitment","volume":"287","author":"Rives","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.113.089649_bib31","doi-asserted-by":"crossref","first-page":"11934","DOI":"10.1073\/pnas.182234399","article-title":"Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist","volume":"99","author":"Roth","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.113.089649_bib32","doi-asserted-by":"crossref","first-page":"22387","DOI":"10.1074\/jbc.M113.476234","article-title":"Functional selectivity of 6\u2019-guanidinonaltrindole (6\u2019-GNTI) at \u03ba-opioid receptors in striatal neurons","volume":"288","author":"Schmid","year":"2013","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.113.089649_bib33","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.pharmthera.2009.05.006","article-title":"30 years of dynorphins\u2014new insights on their functions in neuropsychiatric diseases","volume":"123","author":"Schwarzer","year":"2009","journal-title":"Pharmacol Ther"},{"key":"10.1124\/mol.113.089649_bib34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0165-6147(03)00027-0","article-title":"Salvinorin A: the \u201cmagic mint\u201d hallucinogen finds a molecular target in the kappa opioid receptor","volume":"24","author":"Sheffler","year":"2003","journal-title":"Trends Pharmacol Sci"},{"key":"10.1124\/mol.113.089649_bib35","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s00018-011-0844-x","article-title":"The dynorphin\/\u03ba-opioid receptor system and its role in psychiatric disorders","volume":"69","author":"Tejeda","year":"2012","journal-title":"Cell Mol Life Sci"},{"key":"10.1124\/mol.113.089649_bib36","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ejphar.2008.02.028","article-title":"LPK-26, a novel kappa-opioid receptor agonist with potent antinociceptive effects and low dependence potential","volume":"584","author":"Tao","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/mol.113.089649_bib37","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1097\/00008877-200512000-00010","article-title":"Effects of the long-lasting kappa opioid 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl) ethyl] acetamide in a drug discrimination and warm water tail-withdrawal procedure","volume":"16","author":"Terner","year":"2005","journal-title":"Behav Pharmacol"},{"key":"10.1124\/mol.113.089649_bib38","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nature11085","article-title":"Structure of the nociceptin\/orphanin FQ receptor in complex with a peptide mimetic","volume":"485","author":"Thompson","year":"2012","journal-title":"Nature"},{"key":"10.1124\/mol.113.089649_bib39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/jpet.106.104463","article-title":"Functional selectivity and classical concepts of quantitative pharmacology","volume":"320","author":"Urban","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.113.089649_bib40","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.cell.2013.01.025","article-title":"Conformational ensembles in GPCR activation","volume":"152","author":"Vardy","year":"2013","journal-title":"Cell"},{"key":"10.1124\/mol.113.089649_bib41","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1126\/science.1232808","article-title":"Structural features for functional selectivity at serotonin receptors","volume":"340","author":"Wacker","year":"2013","journal-title":"Science"},{"key":"10.1124\/mol.113.089649_bib42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00213-010-1825-8","article-title":"The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse","volume":"210","author":"Wee","year":"2010","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1124\/mol.113.089649_bib43","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.biopsych.2012.08.014","article-title":"Psychotomimetic effects of kappa opioid receptor agonists","volume":"72","author":"White","year":"2012","journal-title":"Biol Psychiatry"},{"key":"10.1124\/mol.113.089649_bib44","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nature10939","article-title":"Structure of the human \u03ba-opioid receptor in complex with JDTic","volume":"485","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"10.1124\/mol.113.089649_bib45","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1124\/jpet.111.183780","article-title":"Antagonist functional selectivity: 5-HT2A serotonin receptor antagonists differentially regulate 5-HT2A receptor protein level in vivo","volume":"339","author":"Yadav","year":"2011","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.113.089649_bib46","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1021\/bi701476b","article-title":"Galpha-subunits differentially alter the conformation and agonist affinity of kappa-opioid receptors","volume":"47","author":"Yan","year":"2008","journal-title":"Biochemistry"},{"key":"10.1124\/mol.113.089649_bib47","doi-asserted-by":"crossref","first-page":"6898","DOI":"10.1021\/bi900605n","article-title":"Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor","volume":"48","author":"Yan","year":"2009","journal-title":"Biochemistry"},{"key":"10.1124\/mol.113.089649_bib48","doi-asserted-by":"crossref","first-page":"21901","DOI":"10.1074\/jbc.M301905200","article-title":"A direct interaction of PSD-95 with 5-HT2A serotonin receptors regulates receptor trafficking and signal transduction","volume":"278","author":"Xia","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.113.089649_bib49","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1021\/cc9900706","article-title":"Confirmation of primary active substances from high throughput screening of chemical and biological populations: a statistical approach and practical considerations","volume":"2","author":"Zhang","year":"2000","journal-title":"J Comb Chem"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24038471?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24038471?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/mol.113.089649","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T11:18:11Z","timestamp":1739963891000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24038471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["S0026895X24038471"],"URL":"https:\/\/doi.org\/10.1124\/mol.113.089649","relation":{},"ISSN":["0026-895X"],"issn-type":[{"value":"0026-895X","type":"print"}],"subject":[],"published":{"date-parts":[[2014,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification of Novel Functionally Selective \u03ba-Opioid Receptor Scaffolds","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/mol.113.089649","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2013 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}