Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation - PubMed (original) (raw)

Thomas Krahn, Margarete Schön, Maria-L Rodriguez, Horst Antonicek, Jeanette E Schultz, Ralf J Ludwig, Thomas M Zollner, Erwin Bischoff, Klaus-D Bremm, Matthias Schramm, Kerstin Henninger, Roland Kaufmann, Harald P M Gollnick, Christina M Parker, W-Henning Boehncke

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Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation

Michael P Schön et al. Nat Med. 2002 Apr.

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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.

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