8RXM

Galectin-3 in complex with thiogalactoside derivative

This is a non-PDB format compatible entry.

Summary for 8RXM

• Entry DOI: 10.2210/pdb8rxm/pdb
• Descriptor: Galectin-3, 5-bromanyl-3-[(2~{R},3~{R},4~{S},5~{R},6~{R})-4-[4-(4-chloranyl-1,3-thiazol-2-yl)-1,2,3-triazol-1-yl]-6-(hydroxymethyl)-3-methoxy-5-oxidanyl-oxan-2-yl]sulfanyl-pyridine-2-carbonitrile, GLYCEROL, ... (6 entities in total)
• Functional Keywords: galactic, ligand, thiogalactoside derivative, sugar binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 16588.64

Authors

Hakansson, M.,Diehl, C.,Peterson, K.,Zetterberg, F.,Nilsson, U. (deposition date: 2024-02-07, release date: 2025-10-15, Last modification date: 2026-07-01)

Primary citation

Zetterberg, F.R.,Peterson, K.,Nilsson, U.J.,Diehl, C.,Hakansson, M.,Kahl-Knutson, B.,MacKinnon, A.C.,Klein, H.,Leffler, H.,Roper, J.A.,Slack, R.J.,Wachenfeldt, H.V.,Pedersen, A.
An Orally Available Halothiazole Glycomimetic as a Cancer-Targeting Dual Galectin-1 and Galectin-3 Inhibitor.
J.Med.Chem., 69:10494-10514, 2026

PubMed Abstract: Inhibition of several of the 10 hallmarks of cancer (Hanahan and Weinberg) would result in a broader and more durable treatment compared to current single or combination drug treatments. Galectin-1 and galectin-3 have been proposed to together be involved in all 10 hallmarks, suggesting that development of a combined galectin-1/3 inhibitor would be beneficial. Specificity toward galectin-1 or -3 can be modulated using different aryl moieties in 3-(aryl)triazolyl-galactopyranoside derivatives. By combining these findings, a new class of 3-(halothiazolyl)triazolyl derivatives with high affinity for both human galectin-1 and -3 were discovered and optimized with respect to SAR and in vitro ADME parameters, resulting in ( galectin-1/-3 0.027/0.14 μM). Both selective and dual inhibition of galectin-1 and galectin-3 significantly reduces the growth of LL/2 lung cancer cells in a syngeneic mouse model, supporting further development of as a dual inhibitor of galectin-1 and galectin-3.

PubMed: 42052938
DOI: 10.1021/acs.jmedchem.5c03703

Experimental method

X-RAY DIFFRACTION (1.1 Å)