7df6 | pdb_00007df6

Mouse Galectin-3 CRD in complex with novel tetrahydropyran-based thiodisaccharide mimic inhibitor

spinqualitylabelsall models 7df6, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7df6 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: H5O Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LEG3_MOUSE Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis. In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells. Together with TRIM16, coordinates the recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1 and BECN1 in response to damaged endomembranes. Publication Abstract from PubMed Galectin-3 is a member of a family of beta-galactoside-binding proteins. A substantial body of literature reports that galectin-3 plays important roles in cancer, inflammation, and fibrosis. Small-molecule galectin-3 inhibitors, which are generally lactose or galactose-based derivatives, have the potential to be valuable disease-modifying agents. In our efforts to identify novel galectin-3 disaccharide mimics to improve drug-like properties, we found that one of the monosaccharide subunits can be replaced with a suitably functionalized tetrahydropyran ring. Optimization of the structure-activity relationships around the tetrahydropyran-based scaffold led to the discovery of potent galectin-3 inhibitors. Compounds 36, 40, and 45 were selected for further in vivo evaluation. The synthesis, structure-activity relationships, and in vivo evaluation of novel tetrahydropyran-based galectin-3 inhibitors are described. Synthesis, Structure-Activity Relationships, and In Vivo Evaluation of Novel Tetrahydropyran-Based Thiodisaccharide Mimics as Galectin-3 Inhibitors.,Xu L, Hartz RA, Beno BR, Ghosh K, Shukla JK, Kumar A, Patel D, Kalidindi N, Lemos N, Gautam SS, Kumar A, Ellsworth BA, Shah D, Sale H, Cheng D, Regueiro-Ren A J Med Chem. 2021 May 27;64(10):6634-6655. doi: 10.1021/acs.jmedchem.0c02001. Epub, 2021 May 14. PMID:33988358 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Galectin 3D structures

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