{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:24:35Z","timestamp":1771237475926,"version":"3.50.1"},"reference-count":40,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["KO4095\/4-1"],"award-info":[{"award-number":["KO4095\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["KO4095\/5-1"],"award-info":[{"award-number":["KO4095\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.molpha.2025.100081","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:26:02Z","timestamp":1760027162000},"page":"100081","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predicting compounds that interact with the 2 known agonist-induced conformations of the human \u03b21-adrenoceptor"],"prefix":"10.1016","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2371-8202","authenticated-orcid":false,"given":"Jillian G.","family":"Baker","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor Jun Yu","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard G.W.","family":"Proudman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2715-7537","authenticated-orcid":false,"given":"Franziska N.Z.","family":"Giese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4089-614X","authenticated-orcid":false,"given":"Peter","family":"Kolb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.pharmthera.2008.03.009","article-title":"The low-affinity site of the beta1-adrenoceptor and its relevance to cardiovascular pharmacology","volume":"118","author":"Kaumann","year":"2008","journal-title":"Pharmacol Ther"},{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0014-2999(69)90195-2","article-title":"Studies with LB 46, a new beta-receptor blocking drug","volume":"6","author":"Lubawski","year":"1969","journal-title":"Eur J Pharmacol"},{"issue":"6","key":"10.1016\/j.molpha.2025.100081_bib3","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1016\/S0021-9258(18)32689-9","article-title":"CGP-12177. A hydrophilic beta-adrenergic receptor radioligand reveals high affinity binding of agonists to intact cells","volume":"258","author":"Staehelin","year":"1983","journal-title":"J Biol Chem"},{"key":"10.1016\/j.molpha.2025.100081_bib4","first-page":"235","article-title":"Adrenergic receptors of cardiac muscle. Two different mechanisms of beta-blockers as partial agonists. Int. Union of Biochemistry, Symposium No. 52","volume":"23","author":"Kaumann","year":"1973","journal-title":"Acta Physiol. Lat. Am"},{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib5","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/BF00569403","article-title":"beta-Adrenoceptor blocking agents as partial agonists in isolated heart muscle: dissociation of stimulation and blockade","volume":"311","author":"Kaumann","year":"1980","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"2","key":"10.1016\/j.molpha.2025.100081_bib6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/sj.bjp.0704450","article-title":"Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium","volume":"135","author":"Lowe","year":"2002","journal-title":"Br J Pharmacol"},{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib7","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/S0022-3565(25)39150-0","article-title":"Comparative analysis of beta-1 adrenoceptor agonist and antagonist potency and selectivity of cicloprolol, xamoterol and pindolol","volume":"242","author":"Hicks","year":"1987","journal-title":"J Pharmacol Exp Ther"},{"issue":"5","key":"10.1016\/j.molpha.2025.100081_bib8","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/j.1476-5381.1996.tb15285.x","article-title":"Mediation of the positive chronotropic effect of CGP 12177 and cyanopindolol in the pithed rat by atypical beta-adrenoceptors, different from beta 3-adrenoceptors","volume":"117","author":"Malinowska","year":"1996","journal-title":"Br J Pharmacol"},{"issue":"2","key":"10.1016\/j.molpha.2025.100081_bib9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/BF00500912","article-title":"Stimulant and blocking effects of optical isomers of pindolol on the sinoatrial node and trachea of guinea pig. Role of beta-adrenoceptor subtypes in the dissociation between blockade and stimulation","volume":"327","author":"Walter","year":"1984","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"1","key":"10.1016\/j.molpha.2025.100081_bib10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1476-5381.1986.tb11137.x","article-title":"Mode of action of (-)-pindolol on feline and human myocardium","volume":"89","author":"Kaumann","year":"1986","journal-title":"Br J Pharmacol"},{"issue":"1\u20132","key":"10.1016\/j.molpha.2025.100081_bib11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10799899609039938","article-title":"Anomalous behavior of CGP 12177A on beta 1-adrenergic receptors","volume":"16","author":"Pak","year":"1996","journal-title":"J Recept Signal Transduct Res"},{"issue":"8","key":"10.1016\/j.molpha.2025.100081_bib12","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/sj.bjp.0702007","article-title":"Metabolic response to various beta-adrenoceptor agonists in beta3-adrenoceptor knockout mice: evidence for a new beta-adrenergic receptor in brown adipose tissue","volume":"124","author":"Preitner","year":"1998","journal-title":"Br J Pharmacol"},{"issue":"4","key":"10.1016\/j.molpha.2025.100081_bib13","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1124\/mol.53.4.670","article-title":"(-)-CGP 12177 causes cardiostimulation and binds to cardiac putative beta 4-adrenoceptors in both wild-type and beta 3-adrenoceptor knockout mice","volume":"53","author":"Kaumann","year":"1998","journal-title":"Mol Pharmacol"},{"issue":"1","key":"10.1016\/j.molpha.2025.100081_bib14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s002100000336","article-title":"Abolition of (-)-CGP 12177-evoked cardiostimulation in double beta1\/beta2-adrenoceptor knockout mice. Obligatory role of beta1-adrenoceptors for putative beta4-adrenoceptor pharmacology","volume":"363","author":"Kaumann","year":"2001","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"1","key":"10.1016\/j.molpha.2025.100081_bib15","first-page":"17","article-title":"Beta3 receptors mediate relaxation in stomach fundus whereas a fourth beta receptor mediates tachycardia in atria from transgenic beta3 receptor knockout mice","volume":"7","author":"Cohen","year":"2000","journal-title":"Recept Channels"},{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib16","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/S0022-3565(24)39154-2","article-title":"Aryloxypropanolamine and catecholamine ligand interactions with the beta(1)-adrenergic receptor: evidence for interaction with distinct conformations of beta(1)-adrenergic receptors","volume":"294","author":"Konkar","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"issue":"2","key":"10.1016\/j.molpha.2025.100081_bib17","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0026-895X(24)23196-5","article-title":"beta1-adrenergic receptors mediate beta3-adrenergic-independent effects of CGP 12177 in brown adipose tissue","volume":"57","author":"Konkar","year":"2000","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.molpha.2025.100081_bib18","doi-asserted-by":"crossref","first-page":"E199","DOI":"10.1152\/ajpendo.2001.280.2.E199","article-title":"The putative beta4-adrenergic receptor is a novel state of the beta1-adrenergic receptor","volume":"280","author":"Granneman","year":"2001","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"6","key":"10.1016\/j.molpha.2025.100081_bib19","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1124\/mol.63.6.1312","article-title":"Agonist actions of \"beta-blockers\" provide evidence for two agonist activation sites or conformations of the human beta1-adrenoceptor","volume":"63","author":"Baker","year":"2003","journal-title":"Mol Pharmacol"},{"issue":"6","key":"10.1016\/j.molpha.2025.100081_bib20","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s00210-003-0835-z","article-title":"Intrinsic sympathomimetic activity of (-)-pindolol mediated through a (-)-propranolol-resistant site of the beta1-adrenoceptor in human atrium and recombinant receptors","volume":"368","author":"Joseph","year":"2003","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib21","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1124\/jpet.104.082875","article-title":"Site of action of beta-ligands at the human beta1-adrenoceptor","volume":"313","author":"Baker","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"issue":"6","key":"10.1016\/j.molpha.2025.100081_bib22","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1124\/mol.105.015461","article-title":"Evidence for a secondary state of the human beta3-adrenoceptor","volume":"68","author":"Baker","year":"2005","journal-title":"Mol Pharmacol"},{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib23","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/sj.bjp.0704855","article-title":"Pharmacological characterization of CGP 12177 at the human beta(2)-adrenoceptor","volume":"137","author":"Baker","year":"2002","journal-title":"Br J Pharmacol"},{"issue":"5","key":"10.1016\/j.molpha.2025.100081_bib24","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1111\/j.1476-5381.2010.00754.x","article-title":"The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors","volume":"160","author":"Baker","year":"2010","journal-title":"Br J Pharmacol"},{"issue":"5","key":"10.1016\/j.molpha.2025.100081_bib25","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1124\/mol.114.091587","article-title":"Identification of key residues in transmembrane 4 responsible for the secondary, low-affinity conformation of the human \u03b21-adrenoceptor","volume":"85","author":"Baker","year":"2014","journal-title":"Mol Pharmacol"},{"issue":"5","key":"10.1016\/j.molpha.2025.100081_bib26","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/sj.bjp.0705990","article-title":"Impairment of the low-affinity state beta1-adrenoceptor-induced relaxation in spontaneously hypertensive rats","volume":"143","author":"Mallem","year":"2004","journal-title":"Br J Pharmacol"},{"issue":"8","key":"10.1016\/j.molpha.2025.100081_bib27","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.peptides.2005.03.018","article-title":"Low-affinity state beta1-adrenoceptor-induced vasodilation in SHR","volume":"26","author":"Mallem","year":"2005","journal-title":"Peptides"},{"issue":"1","key":"10.1016\/j.molpha.2025.100081_bib28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2460\/ajvr.2000.61.57","article-title":"Acute cardiovascular effects and pharmacokinetics of carvedilol in healthy dogs","volume":"61","author":"Sawangkoon","year":"2000","journal-title":"Am J Vet Res"},{"issue":"12","key":"10.1016\/j.molpha.2025.100081_bib29","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1096\/fj.11-192435","article-title":"Predicting in vivo cardiovascular properties of \u03b2-blockers from cellular assays: a quantitative comparison of cellular and cardiovascular pharmacological responses","volume":"25","author":"Baker","year":"2011","journal-title":"FASEB J"},{"key":"10.1016\/j.molpha.2025.100081_bib30","author":"Mistry"},{"key":"10.1016\/j.molpha.2025.100081_bib31","author":"Mistry"},{"issue":"1","key":"10.1016\/j.molpha.2025.100081_bib32","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1038\/s41467-022-29609-6","article-title":"The pocketome of G-protein-coupled receptors reveals previously untargeted allosteric sites","volume":"13","author":"Hedderich","year":"2022","journal-title":"Nat Commun"},{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib33","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J Mol Biol"},{"issue":"Web Server issue","key":"10.1016\/j.molpha.2025.100081_bib34","doi-asserted-by":"crossref","first-page":"W270","DOI":"10.1093\/nar\/gkr366","article-title":"SwissDock, a protein-small molecule docking web service based on EADock DSS","volume":"39","author":"Grosdidier","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.molpha.2025.100081_bib35","series-title":"2024.0601. Chemical Computing Group ULC, 910-1010 Sherbrooke St. W., Montreal, QC H3A 2R7","year":"2025"},{"issue":"4","key":"10.1016\/j.molpha.2025.100081_bib36","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1021\/acs.jcim.2c01253","article-title":"ZINC-22\u2500a free multi-billion-scale database of tangible compounds for ligand discovery","volume":"63","author":"Tingle","year":"2023","journal-title":"J Chem Inf Model"},{"issue":"3","key":"10.1016\/j.molpha.2025.100081_bib37","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/sj.bjp.0706048","article-title":"The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors","volume":"144","author":"Baker","year":"2005","journal-title":"Br J Pharmacol"},{"issue":"1","key":"10.1016\/j.molpha.2025.100081_bib38","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1124\/jpet.106.113589","article-title":"A comparison of the antagonist affinities for the Gi- and Gs-coupled states of the human adenosine A1-receptor","volume":"320","author":"Baker","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"10.1016\/j.molpha.2025.100081_bib39","first-page":"48","article-title":"Some quantitative uses of drug antagonists","volume":"14","author":"Arunlakshana","year":"1959","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.molpha.2025.100081_bib40","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1476-5381.1956.tb00006.x","article-title":"A modification of receptor theory","volume":"11","author":"Stephenson","year":"1956","journal-title":"Br J Pharmacol Chemother"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X25157416?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X25157416?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T08:07:29Z","timestamp":1766131649000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X25157416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["S0026895X25157416"],"URL":"https:\/\/doi.org\/10.1016\/j.molpha.2025.100081","relation":{},"ISSN":["0026-895X"],"issn-type":[{"value":"0026-895X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Predicting compounds that interact with the 2 known agonist-induced conformations of the human \u03b21-adrenoceptor","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molpha.2025.100081","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics.","name":"copyright","label":"Copyright"}],"article-number":"100081"}}