title: Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation.
abstract: Specific interference with molecular mechanisms guiding tissue localization of leukocytes may be of great utility for selective immunosuppressive therapies. We have discovered and characterized efomycines, a new family of selective small-molecule inhibitors of selectin functions. Members of this family significantly inhibited leukocyte adhesion in vitro. Efomycine M, which was nontoxic and showed the most selective inhibitory effects on selectin-mediated leukocyte-endothelial adhesion in vitro, significantly diminished rolling in mouse ear venules in vivo as seen by intravital microscopy. In addition, efomycine M alleviated cutaneous inflammation in two complementary mouse models of psoriasis, one of the most common chronic inflammatory skin disorders. Molecular modeling demonstrated a spatial conformation of efomycines mimicking naturally occurring selectin ligands. Efomycine M might be efficacious in the treatment of human inflammatory disorders through a similar mechanism.
authors.affiliation: Department of Dermatology, Otto-von-Guericke-University, Magdeburg, Germany. michael.schoen@medizin.uni-magdeburg.de
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
authors.forename: Thomas
authors.initials: T
authors.lastname: Krahn
authors.forename: Margarete
authors.initials: M
authors.lastname: Schön
authors.forename: Maria-L
authors.initials: ML
authors.lastname: Rodriguez
authors.forename: Horst
authors.initials: H
authors.lastname: Antonicek
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Schultz
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Zollner
authors.forename: Erwin
authors.initials: E
authors.lastname: Bischoff
authors.forename: Klaus-D
authors.initials: KD
authors.lastname: Bremm
authors.forename: Matthias
authors.initials: M
authors.lastname: Schramm
authors.forename: Kerstin
authors.initials: K
authors.lastname: Henninger
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: Harald P M
authors.initials: HP
authors.lastname: Gollnick
authors.forename: Christina M
authors.initials: CM
authors.lastname: Parker
authors.forename: W-Henning
authors.initials: WH
authors.lastname: Boehncke
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D019040:E-Selectin / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects*; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D000080506:Sialyl Lewis X Antigen; D016038:Skin Transplantation; D013302:Streptomyces / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019040:E-Selectin; D018942:Macrolides; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; C453219:efomycine M