Galectin-3 (Gal-3), a member of the β-galactoside-binding
protein family, is implicated in a wide variety of human diseases.
Identification of Gal-3 inhibitors with the right combination of potency
(against
both human and mouse Gal-3) and pharmacokinetic properties to fully
evaluate the potential of Gal-3 for therapeutic intervention has been
a major challenge due to the characteristics of its binding pocket:
high hydrophilicity and key structural differences between human Gal-3
and the mouse ortholog. We report the discovery of a novel series
of monosaccharide-based, highly potent, and orally bioavailable inhibitors
of human and mouse Gal-3. The novel monosaccharide derivatives proved
to be selective for Gal-3, the only member of the chimeric type of
galectins, over Gal-1 and Gal-9, representative of the prototype and
tandem-repeat type of galectins, respectively. The proposed binding
mode for the newly identified ligands was confirmed by an X-ray cocrystal
structure of a representative analogue bound to Gal-3 protein.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.