title: Discovery of novel phenoxazinone derivatives as DKK1/LRP6 interaction inhibitors: Synthesis, biological evaluation and structure-activity relationships.
abstract: Amino derivatives of NCI8642 were synthesized and evaluated as inhibitors of DKK1/LRP6 interactions. The new inhibitors were able to activate the Wnt signaling pathway as indicated by the increased levels of β-catenin, and decrease the DKK1-induced Tau phosphorylation at serine 396.
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Savvas
authors.initials: S
authors.lastname: Thysiadis
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Mpousis
authors.affiliation: Division of Animal and Human Physiology, Department of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, Ilisia 15784, Greece.
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Avramidis
authors.affiliation: Department of Pharmacy, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Katsamakas
authors.affiliation: Division of Animal and Human Physiology, Department of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, Ilisia 15784, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Balomenos
authors.affiliation: VIB Discovery Sciences Bio-incubator Leuven, Gaston Geenslan 1, 3001 Leuven, Belgium.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Remelli
authors.affiliation: Division of Animal and Human Physiology, Department of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, Ilisia 15784, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Efthimiopoulos
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Sarli
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000378:metabolism*; D008958:Models, Molecular; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D060066:Protein Interaction Maps / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D010078:Oxazines; D051153:Wnt Proteins; D051176:beta Catenin; C020456:phenoxazinone
keywords: DKK1/LRP6 interaction inhibitors; NCI8642; Phenoxazinone; Tau phosphorylation inhibitors; Wnt signaling