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  • Title: Target Selectivity of FimH Antagonists.
    Author: Scharenberg M, Schwardt O, Rabbani S, Ernst B.
    Journal: J Med Chem; 2012 Nov 26; 55(22):9810-6. PubMed ID: 23088608.
    Abstract:
    Mannose-based FimH antagonists are considered new therapeutics for the treatment of urinary tract infections (UTIs). They prevent the adhesion of uropathogenic Escherichia coli (UPEC) to urothelial cell surfaces triggered by the lectin FimH, which is located at the tip of bacterial type 1 pili. Because all reported FimH antagonists are α-d-mannosides, they are also potential ligands of mannose receptors of the human host system. We therefore investigated the selectivity range of five FimH antagonists belonging to different compound families by comparing their affinities for FimH and eight human mannose receptors. On the basis of the detected selectivity range of approximately 5 orders of magnitude, no adverse side effects resulting from nonselective binding to the human receptors have to be expected. FimH antagonists can therefore be further considered as potential therapeutics for the treatment of UTI.
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