{"entity": "publication", "iuid": "5f3f0f08217849009a2a448978b3c931", "timestamp": "2026-09-30T18:50:38.579Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5f3f0f08217849009a2a448978b3c931.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5f3f0f08217849009a2a448978b3c931"}}, "title": "SAG1.3-derived Frizzled-targeting small-molecule compounds.", "authors": [{"family": "Gr\u00e4tz", "given": "Lukas", "initials": "L"}, {"family": "Turku", "given": "Ainoleena", "initials": "A"}, {"family": "Kozielewicz", "given": "Pawel", "initials": "P"}, {"family": "Bowin", "given": "Carl-Fredrik", "initials": "CF"}, {"family": "Scharf", "given": "Magdalena M", "initials": "MM"}, {"family": "Voss", "given": "Jan H", "initials": "JH"}, {"family": "Kinsolving", "given": "Julia", "initials": "J"}, {"family": "Shekhani", "given": "Rawan", "initials": "R"}, {"family": "Oliva-Vilarnau", "given": "Nuria", "initials": "N"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "K\u00f6rber", "given": "Marlies", "initials": "M"}, {"family": "Lauschke", "given": "Volker M", "initials": "VM"}, {"family": "L\u00f6ber", "given": "Stefan", "initials": "S"}, {"family": "Gmeiner", "given": "Peter", "initials": "P"}, {"family": "Schulte", "given": "Gunnar", "initials": "G"}], "type": "journal article", "published": "2025-11-00", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "301", "issue": "11", "pages": "110751", "issn-l": "0021-9258"}, "abstract": "Exaggerated Wingless/Int1 (WNT)-Frizzled (FZD) signaling contributes to pathologies, including fibrosis and different forms of cancer. Thus, targeting FZDs as WNT receptors for therapeutic purposes constitutes a promising intervention if the imminent risk of unwanted side effects caused by the involvement of WNT-FZD signaling in stem cell regulation and tissue homeostasis can be controlled. Here, we derivatize SAG1.3 (SMO agonist), which acts through FZD6 as a partial agonist. Screening of SAG1.3 derivatives identified compound 11 that competed with BODIPY (boron-dipyrromethene)-cyclopamine binding at different FZDs and inhibited WNT-induced FZD dynamics and \u03b2-catenin signaling in human embryonic kidney 293 (HEK293) cells. Furthermore, compound 11 blocked WNT-3A-induced LGR5 gene expression in human primary hepatocyte spheroids and reduced the viability of RNF43-mutated but not RNF43-wildtype pancreatic cancer cells. Based on our data, we suggest that compound 11 acts on FZDs to limit WNT- and WNT-surrogate-induced receptor dynamics, providing a valid proof of concept for targeting FZDs with small-molecule compounds.", "doi": "10.1016/j.jbc.2025.110751", "pmid": "40992662", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12605013"}, {"db": "pii", "key": "S0021-9258(25)02603-1"}], "notes": [], "created": "2026-09-23T13:19:16.426Z", "modified": "2026-09-23T13:19:16.450Z"}