Summary for 8RMU
| Entry DOI | 10.2210/pdb8rmu/pdb |
| Descriptor | Galectin-3, (2~{R},3~{R},4~{S},5~{R},6~{R})-~{N}-[3,5-bis(chloranyl)phenyl]-6-(hydroxymethyl)-3-methoxy-5-oxidanyl-~{N}-[(1~{S},2~{S})-2-oxidanylcyclopentyl]-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxane-2-carboxamide, THIOCYANATE ION, ... (4 entities in total) |
| Functional Keywords | inhibitor, fibrosis, sugar binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 16579.84 |
| Authors | Mac Sweeney, A.,Sager, C. (deposition date: 2024-01-08, release date: 2025-01-29, Last modification date: 2025-06-04) |
| Primary citation | Zumbrunn, C.,Remen, L.,Sager, C.P.,Grisostomi, C.,Stamm, C.,Krusi, D.,Glutz, S.,Schmidt, G.,Nayler, O.,Iglarz, M.,Mac Sweeney, A.,Chambovey, A.,Muller, M.,Mueller, C.,Bourquin, G.,Meyer, S.,Huhn, E.,Cattaneo, C.,Vercauteren, M.,Gatfield, J.,Bolli, M.H. Discovery of Galactopyranose-1-carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin-3 Inhibitors. Chemmedchem, 20:e202401012-e202401012, 2025 Cited by PubMed Abstract: Galectin-3 (Gal-3), a β-galactoside-binding lectin, is implicated in diverse cellular functions ranging from immune response modulation to tissue homeostasis. Notably, increased Gal-3 expression has been linked to the progression of numerous diseases, including cancer, fibrosis, and cardiovascular disorders, underscoring its potential as a therapeutic target. Small molecule inhibitors have been discovered and are valuable tools to study such diseases. We report here the discovery of novel, galactose-based, small molecule inhibitors such as compound 12 which are orally bioavailable and show efficacy in a mouse model of acute liver injury and fibrosis (CCl model). The use of structure-based drug design (docking of a virtual library of amides based on acid 2) was key in the process towards potent, nanomolar inhibitors. PubMed: 40071533DOI: 10.1002/cmdc.202401012 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.2 Å) |
Structure validation
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