title: Discovery of potent cell migration inhibitors through total synthesis: lessons from structure-activity studies of (+)-migrastatin.
abstract: Synthesis of highly active migrastatin-based tumor migration cell inhibitors has been accomplished. Our flexible and concise total synthesis of migrastatin has allowed us to explore otherwise inaccessible migrastatin-derived structural motifs. This effort has resulted in the discovery of analogues with tumor cell migration inhibitory activity 3 orders of magnitude higher than that of the natural product.
authors.affiliation: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
authors.forename: Jón T
authors.initials: JT
authors.lastname: Njardarson
authors.forename: Christoph
authors.initials: C
authors.lastname: Gaul
authors.forename: Dandan
authors.initials: D
authors.lastname: Shan
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Huang
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015195:Drug Design; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018942:Macrolides; D051379:Mice; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D020533:Angiogenesis Inhibitors; D007783:Lactones; D018942:Macrolides; D010881:Piperidones; C418199:migrastatin