title: Potent small molecule Hedgehog agonists induce VEGF expression in vitro.
abstract: Here, we describe the synthesis, SAR studies as well as biological investigations of the known Hedgehog signaling agonist SAG and a small library of its analogues. The SAG and its derivatives were analyzed for their potency to activate the expression of the Hh target gene Gli1 in a reporter gene assay. By analyzing SAR important molecular descriptors for Gli1 activation have been identified. SAG as well as compound 10c proven to be potent activators of VEGF expression in cultivated dermal fibroblasts. Importantly and in contrast to SAG, derivative 10c displayed no toxicity in concentrations up to 250 μm.
authors.affiliation: Universität Leipzig, Fakultät für Chemie und Mineralogie, Institut für Organische Chemie, Johannisallee 29, 04103 Leipzig, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Seifert
authors.forename: Anita
authors.initials: A
authors.lastname: Büttner
authors.forename: Stephan
authors.initials: S
authors.lastname: Rigol
authors.forename: Nicole
authors.initials: N
authors.lastname: Eilert
authors.forename: Elke
authors.initials: E
authors.lastname: Wandel
authors.forename: Athanassios
authors.initials: A
authors.lastname: Giannis
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D053823:Hedgehog Proteins / Q000819:agonists* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D054852:Small Molecule Libraries; D042461:Vascular Endothelial Growth Factor A