7ZQX
Human galectin-3c in complex with a galactose derivative
Summary for 7ZQX
| Entry DOI | 10.2210/pdb7zqx/pdb |
| Descriptor | Galectin-3, GLYCEROL, THIOCYANATE ION, ... (7 entities in total) |
| Functional Keywords | inhibitor, complex, sugar binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 16496.91 |
| Authors | Zetterberg, F.,Nilsson, U.J.,Hakansson, M.,Logan, D.T. (deposition date: 2022-05-03, release date: 2022-11-02, Last modification date: 2024-01-31) |
| Primary citation | Zetterberg, F.R.,MacKinnon, A.,Brimert, T.,Gravelle, L.,Johnsson, R.E.,Kahl-Knutson, B.,Leffler, H.,Nilsson, U.J.,Pedersen, A.,Peterson, K.,Roper, J.A.,Schambye, H.,Slack, R.J.,Tantawi, S. Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease. J.Med.Chem., 65:12626-12638, 2022 Cited by PubMed Abstract: Galectin-3 is a carbohydrate-binding protein central to regulating mechanisms of diseases such as fibrosis, cancer, metabolic, inflammatory, and heart disease. We recently found a high affinity (nM) thiodigalactoside GB0139 which currently is in clinical development (PhIIb) as an inhaled treatment of idiopathic pulmonary fibrosis. To enable treatment of systemically galectin-3 driven disease, we here present the first series of selective galectin-3 inhibitors combining high affinity (nM) with oral bioavailability. This was achieved by optimizing galectin-3 specificity and physical chemical parameters for a series of disubstituted monogalactosides. Further characterization showed that this class of compounds reduced profibrotic gene expression in liver myofibroblasts and displayed antifibrotic activity in CCl-induced liver fibrosis and bleomycin-induced lung fibrosis mouse models. On the basis of the overall pharmacokinetic, pharmacodynamic, and safety profile, GB1211 was selected as the clinical candidate and is currently in phase IIa clinical trials as a potential therapy for liver cirrhosis and cancer. PubMed: 36154172DOI: 10.1021/acs.jmedchem.2c00660 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.05 Å) |
Structure validation
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