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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors.

An early step of the inflammatory response, the rolling of leukocytes on activated endothelial cells, is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialy Lewisx is a ligand for E-, P-, and L-selectin and therefore serves as a lead structure for the development of analogues. A combination of synthesis and structure-based design allowed rapid optimization. The current lead 2a was evaluated in our E-selectin cell flow chamber assay where it proved to inhibit rolling and adhesion with an IC50 of 28+/-7 microM. The assays used are predictive for the in vivo efficacy of test compounds as shown for 2a in a proteose peptone induced peritonitis model of acute inflammation in mice.[1]


  1. A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors. Ulbrich, H.K., Luxenburger, A., Prech, P., Eriksson, E.E., Soehnlein, O., Rotzius, P., Lindbom, L., Dannhardt, G. J. Med. Chem. (2006) [Pubmed]
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