9S62

Galectin-3 in complex with N-[4-O-(beta-d-Galactopyranosyl)-beta-d-glucopyranosyl]-N-(3-carboxyphenyl)acetamide

This is a non-PDB format compatible entry.

Summary for 9S62

• Entry DOI: 10.2210/pdb9s62/pdb
• Descriptor: Galectin-3, beta-D-galactopyranose-(1-4)-1,5-anhydro-D-glucitol, 3-acetamidobenzoic acid, ... (4 entities in total)
• Functional Keywords: sugar binding protein, complex
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 16337.71

Authors

Pachl, P. (deposition date: 2025-07-30, release date: 2025-11-19, Last modification date: 2025-12-10)

Primary citation

Zyka, J.,Kozak, J.,Vanekova, L.,Pimkova Polidarova, M.,Prouza, V.,Habanova, N.,Strmen, T.,Zavrel, M.,Pachl, P.,Choutka, J.,Grantz Saskova, K.,Brazdova, A.,Parkan, K.,Pohl, R.
N -Aryl- N -Lactosylamides as Potent and Highly Selective Inhibitors of Galectin-3 with Antifibrotic Activity.
J.Med.Chem., 68:24624-24648, 2025

PubMed 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 -aryl--(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 , binds to Gal-3 with excellent affinity ( = 5.7 nM) and selectivity (390-fold over Gal-1). Further in vitro characterization of this compound demonstrated high metabolic stability and no cytotoxicity (CC > 300 μM). Compound effectively engages Gal-3 with greater activity in macrophage-like than monocyte-like THP1 cells, without affecting inflammation via LPS-induced release of TNFα. In TGFβ-stimulated LX2 hepatic stellate cells, it downregulates profibrotic signaling as assessed by the reduced expression of , , and . These findings implicate compound as a promising candidate for further preclinical development in the context of fibrotic disease.

PubMed: 41217252
DOI: 10.1021/acs.jmedchem.5c02604

Experimental method

X-RAY DIFFRACTION (1.059 Å)