title: Studies directed toward the elucidation of the pharmacophore of steroid-based Sonic Hedgehog signaling inhibitors.
abstract: Previous work from our laboratory has established that the readily available steroid-based analog 2 of cyclopamine 1 is, like 1, a highly potent inhibitor of Hedgehog signaling. The first structure-activity relationship studies on 2, i.e., the synthesis and biological evaluation of both the C-17 epi analog 4 and the C-3 deoxy analog 11, both of which are more potent than cyclopamine 1, are described. The implications of these results for the emerging pharmacophore of these Sonic Hedgehog signaling inhibitors are discussed.
authors: Department of Chemistry, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: André K
authors: AK
authors: Isaacs
authors: Chaomei
authors: C
authors: Xiang
authors: Valérie
authors: V
authors: Baubet
authors: Nadia
authors: N
authors: Dahmane
authors: Jeffrey D
authors: JD
authors: Winkler
mesh_terms: D002460:Cell Line; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects*; D013256:Steroids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D013256:Steroids; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1