{"entity": "researcher", "timestamp": "2026-08-05T20:24:29.839Z", "family": "Sarret", "given": "Philippe", "initials": "P", "orcid": "0000-0002-7627-701X", "affiliations": ["Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Institute de Pharmacologie de Sherbrooke, Universit\u00e9 de Sherbrooke, Sherbrooke, QC, Canada. philippe.sarret@usherbrooke.ca."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/4511aa2978af482ab9492f01c521b5bd.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/4511aa2978af482ab9492f01c521b5bd"}}, "publications": [{"entity": "publication", "iuid": "023ffcdeef6f4cfdb03af2b67df53148", "links": {"self": {"href": "https://publications.scilifelab.se/publication/023ffcdeef6f4cfdb03af2b67df53148.json"}, "display": {"href": "https://publications.scilifelab.se/publication/023ffcdeef6f4cfdb03af2b67df53148"}}, "title": "Docking of virtual libraries identifies small-molecule agonists of neurotensin receptors with analgesic activity.", "authors": [{"family": "Panel", "given": "Nicolas", "initials": "N", "orcid": "0000-0001-8782-0586", "researcher": {"href": "https://publications.scilifelab.se/researcher/24a74eba4e5c4234b0f21675c2294f04.json"}}, {"family": "Vo", "given": "Duy Duc", "initials": "DD"}, {"family": "H\u00fcbner", "given": "Harald", "initials": "H", "orcid": "0000-0002-7892-599X", "researcher": {"href": "https://publications.scilifelab.se/researcher/76a33c1eae424518885794e3a10bec3a.json"}}, {"family": "Deluigi", "given": "Mattia", "initials": "M", "orcid": "0000-0001-9132-2774", "researcher": {"href": "https://publications.scilifelab.se/researcher/d69b69c3083b4edaa151460909d09d52.json"}}, {"family": "Pach", "given": "Szymon", "initials": "S", "orcid": "0000-0001-6109-7123", "researcher": {"href": "https://publications.scilifelab.se/researcher/0549d10cbdc24117a6ae0d0a10617674.json"}}, {"family": "B\u00e9lair", "given": "F\u00e9lix", "initials": "F"}, {"family": "Weikert", "given": "Dorothee", "initials": "D", "orcid": "0000-0003-2259-9002", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a665be80cf94398b96c3797ba324815.json"}}, {"family": "Klenk", "given": "Christoph", "initials": "C", "orcid": "0000-0001-5199-7144", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf7a1da857fb403bb9c8c5309f3c4f4e.json"}}, {"family": "Hilge", "given": "Mark", "initials": "M"}, {"family": "Shiva", "given": "Niharika", "initials": "N", "orcid": "0009-0007-7951-4598", "researcher": {"href": "https://publications.scilifelab.se/researcher/2af9534c74134de3b743ed89b01d0a2b.json"}}, {"family": "Brochu", "given": "Isabelle", "initials": "I"}, {"family": "Longpr\u00e9", "given": "Jean-Michel", "initials": "JM", "orcid": "0000-0003-3985-2318", "researcher": {"href": "https://publications.scilifelab.se/researcher/eff617d76bd14603a193a60591e3000d.json"}}, {"family": "B\u00e4llgren", "given": "Frida", "initials": "F", "orcid": "0009-0007-4885-9120", "researcher": {"href": "https://publications.scilifelab.se/researcher/911997685ed347199dbf0b870df849ea.json"}}, {"family": "Saleh", "given": "Aljona", "initials": "A", "orcid": "0009-0002-2121-043X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c469c0a07dc746c2a16b122c2269480c.json"}}, {"family": "Hu", "given": "Huabin", "initials": "H"}, {"family": "Kapla", "given": "Jon", "initials": "J", "orcid": "0000-0003-3328-1921", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6f10ed4144348d59541a02d6e17daa2.json"}}, {"family": "Kampen", "given": "Stefanie", "initials": "S"}, {"family": "Cabeza de Vaca", "given": "Israel", "initials": "I", "orcid": "0000-0002-6208-1091", "researcher": {"href": "https://publications.scilifelab.se/researcher/65628edbdaa448b8ab37d5eb4e100aee.json"}}, {"family": "Kihlberg", "given": "Jan", "initials": "J", "orcid": "0000-0002-4205-6040", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9805d4f39cc48f79a6e6ba076917021.json"}}, {"family": "Wettschureck", "given": "Nina", "initials": "N", "orcid": "0000-0001-6858-1460", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa8eab17eed54b85a233fe74447556a8.json"}}, {"family": "Sarret", "given": "Philippe", "initials": "P", "orcid": "0000-0002-7627-701X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4511aa2978af482ab9492f01c521b5bd.json"}}, {"family": "Pl\u00fcckthun", "given": "Andreas", "initials": "A", "orcid": "0000-0003-4191-5306", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f67a65bf469443a89665bd244bfd0f7.json"}}, {"family": "Gmeiner", "given": "Peter", "initials": "P", "orcid": "0000-0002-4127-197X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8385c6b025fe40e7b8e2f4855625a666.json"}}, {"family": "Carlsson", "given": "Jens", "initials": "J", "orcid": "0000-0003-4623-2977", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7d91087358e46e38bb1b7110dc0b214.json"}}], "type": "journal article", "published": "2026-07-22", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "17", "issue": "1", "issn-l": "2041-1723"}, "abstract": "Peptide-activated G protein-coupled receptors (GPCRs) play crucial roles in numerous diseases, but remain difficult therapeutic targets due to the challenges in developing small-molecule drugs. Here, we explore structure-based strategies to identify small-molecule agonists of neurotensin (NTS) receptors, which hold promise for developing non-opioid analgesics. Chemical libraries of drug-like molecules are first designed based on a receptor-peptide complex, and then 14.5 million compounds are computationally docked to the orthosteric binding site of the NTS1 receptor. A set of 39 top-ranked compounds is synthesized, and seven of these are experimentally confirmed to activate the NTS1 receptor. Structure-guided optimization yields NTS1 ligands with signaling signatures distinct from the endogenous peptide, and these compounds also exhibit high affinity for the NTS2 receptor. High-resolution crystal structures of two agonists bound to the NTS1 receptor confirm predicted binding modes and reveal key determinants of activation. In vivo, the compounds produce robust antinociception in rodents without inducing hypotension, consistent with a contribution of NTS2 receptor activity. To facilitate broader application of our virtual screening approach to peptide-binding GPCRs, we provide access to tailored chemical libraries containing billions of readily synthesizable compounds.", "doi": "10.1038/s41467-026-74990-1", "pmid": "42486867", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13392031"}, {"db": "pii", "key": "10.1038/s41467-026-74990-1"}], "notes": [], "created": "2026-08-04T11:59:25.332Z", "modified": "2026-08-04T11:59:29.136Z"}]}