<i>N</i>-Aryl-<i>N</i>-Lactosylamides as Potent and Highly Selective Inhibitors of Galectin-3 with Antifibrotic Activity.

ABSTRACT: Galectin-3 (Gal-3) is a galactose-binding lectin involved in pathologies such as inflammation, fibrosis, heart disease, and tumor progression. Here, we report N-aryl-N-(thio)lactosylamides as a novel class of Gal-3 inhibitors. A structure-activity study identified 6-carboxyindol-4-yl amide as a key pharmacophoric motif within this series. The most potent inhibitor based on this motif, compound 11, binds to Gal-3 with excellent affinity (K_d = 5.7 nM) and selectivity (390-fold over Gal-1). Further in vitro characterization of this compound demonstrated high metabolic stability and no cytotoxicity (CC₅₀ > 300 μM). Compound 11 effectively engages Gal-3 with greater activity in macrophage-like than monocyte-like THP1 cells, without affect

SUBMITTER: Zyka J 

PROVIDER: S-EPMC12670426 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature