Document Report Card

ID: ALA1137388

Journal: J Med Chem

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

Authors: Ulbrich HK, Luxenburger A, Prech P, Eriksson EE, Soehnlein O, Rotzius P, Lindbom L, Dannhardt G.

Abstract: 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.

CiteXplore: 17004713

DOI: 10.1021/jm060468y