{"entity": "publication", "iuid": "0555aec1b5af470fbd63c4046edc0f86", "timestamp": "2026-08-20T20:43:07.734Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0555aec1b5af470fbd63c4046edc0f86.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0555aec1b5af470fbd63c4046edc0f86"}}, "title": "GRK-biased adrenergic agonists for the treatment of type 2 diabetes and obesity.", "authors": [{"family": "Motso", "given": "Aikaterini", "initials": "A"}, {"family": "Pelcman", "given": "Benjamin", "initials": "B"}, {"family": "Kalinovich", "given": "Anastasia", "initials": "A"}, {"family": "Kahlous", "given": "Nour Aldin", "initials": "NA"}, {"family": "Bokhari", "given": "Muhammad Hamza", "initials": "MH"}, {"family": "Dehvari", "given": "Nodi", "initials": "N"}, {"family": "Halleskog", "given": "Carina", "initials": "C"}, {"family": "Waara", "given": "Erik", "initials": "E"}, {"family": "de Jong", "given": "Jasper", "initials": "J"}, {"family": "Cheesman", "given": "Elizabeth", "initials": "E"}, {"family": "Kallenberg", "given": "Christine", "initials": "C"}, {"family": "Yakala", "given": "Gopala Krishna", "initials": "GK"}, {"family": "Murad", "given": "Praerona", "initials": "P"}, {"family": "Wetterdal", "given": "Erika", "initials": "E"}, {"family": "Andersson", "given": "Pia", "initials": "P"}, {"family": "van Beek", "given": "Sten", "initials": "S"}, {"family": "Sandstr\u00f6m", "given": "Anna", "initials": "A"}, {"family": "Alleluia", "given": "Diane Natacha", "initials": "DN"}, {"family": "Talamonti", "given": "Emanuela", "initials": "E"}, {"family": "Youhanna", "given": "Sonia", "initials": "S"}, {"family": "Sabatier", "given": "Pierre", "initials": "P"}, {"family": "Koenig", "given": "Claire", "initials": "C"}, {"family": "Willems", "given": "Sabine", "initials": "S"}, {"family": "Kemas", "given": "Aurino M", "initials": "AM"}, {"family": "Hutchinson", "given": "Dana S", "initials": "DS"}, {"family": "Ham", "given": "Seungmin", "initials": "S"}, {"family": "Gr\u00e4tz", "given": "Lukas", "initials": "L"}, {"family": "Voss", "given": "Jan", "initials": "J"}, {"family": "Marchan-Alvarez", "given": "Jose G", "initials": "JG"}, {"family": "Priede", "given": "Martins", "initials": "M"}, {"family": "Jaunsleine", "given": "Krista", "initials": "K"}, {"family": "Spura", "given": "Jana", "initials": "J"}, {"family": "Kovada", "given": "Vadims", "initials": "V"}, {"family": "Supe", "given": "Linda", "initials": "L"}, {"family": "Stoddart", "given": "Leigh A", "initials": "LA"}, {"family": "Holliday", "given": "Nicholas D", "initials": "ND"}, {"family": "Newton", "given": "Phillip T", "initials": "PT"}, {"family": "Pillon", "given": "Nicolas J", "initials": "NJ"}, {"family": "Schulte", "given": "Gunnar", "initials": "G"}, {"family": "Summers", "given": "Roger J", "initials": "RJ"}, {"family": "Mutule", "given": "Ilga", "initials": "I"}, {"family": "Suna", "given": "Edgars", "initials": "E"}, {"family": "Olsen", "given": "Jesper V", "initials": "JV"}, {"family": "Molenaar", "given": "Peter", "initials": "P"}, {"family": "Carlsson", "given": "Jens", "initials": "J"}, {"family": "Lauschke", "given": "Volker M", "initials": "VM"}, {"family": "Wright", "given": "Shane C", "initials": "SC"}, {"family": "Bengtsson", "given": "Tore", "initials": "T"}], "type": "journal article", "published": "2025-09-18", "journal": {"title": "Cell", "issn": "1097-4172", "volume": "188", "issue": "19", "pages": "5142-5156.e23", "issn-l": "0092-8674"}, "abstract": "Biased agonism of G protein-coupled receptors (GPCRs) offers potential for safer medications. Current efforts have explored the balance between G proteins and \u03b2-arrestin; however, other transducers like GPCR kinases (GRKs) remain understudied. GRK2 is essential for \u03b22 adrenergic receptor (\u03b22AR)-mediated glucose uptake, but \u03b22AR agonists are considered poor clinical candidates for glycemic management due to Gs/cyclic AMP (cAMP)-induced cardiac side effects and \u03b2-arrestin-dependent desensitization. Using ligand-based virtual screening and chemical evolution, we developed pathway-selective agonists of \u03b22AR that prefer GRK coupling. These compounds perform well in preclinical models of hyperglycemia and obesity and demonstrate a lower potential for cardiac and muscular side effects compared with standard \u03b22-receptor agonists and incretin mimetics, respectively. Furthermore, the lead candidate showed favorable pharmacokinetics and was well tolerated in a placebo-controlled clinical trial. GRK-biased \u03b22AR partial agonists are thus promising oral alternatives to injectable incretin mimetics used in the treatment of type 2 diabetes and obesity.", "doi": "10.1016/j.cell.2025.05.042", "pmid": "40555230", "labels": [], "xrefs": [{"db": "pii", "key": "S0092-8674(25)00630-0"}], "notes": [], "created": "2026-08-20T06:50:41.825Z", "modified": "2026-08-20T06:50:41.873Z"}