9FDC

Co-crystal structure of Galectin-3 with an inhibitor

これはPDB形式変換不可エントリーです。

9FDC の概要

• エントリーDOI: 10.2210/pdb9fdc/pdb
• 分子名称: Galectin-3, NONAETHYLENE GLYCOL, (2~{R},3~{R},4~{S},5~{R},6~{R})-~{N}-[3,5-bis(chloranyl)phenyl]-6-(hydroxymethyl)-~{N}-methyl-3,5-bis(oxidanyl)-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxane-2-carboxamide, ... (5 entities in total)
• 機能のキーワード: inhibitor, sugar binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16720.93

構造登録者

Mac Sweeney, A. (登録日: 2024-05-16, 公開日: 2025-03-26, 最終更新日: 2025-06-04)

主引用文献

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

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 (CCl4 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: 40071533
DOI: 10.1002/cmdc.202401012

実験手法

X-RAY DIFFRACTION (1.78 Å)