| Autor: |
Fredrik R. Zetterberg, Alison MacKinnon, Thomas Brimert, Lise Gravelle, Richard E. Johnsson, Barbro Kahl-Knutson, Hakon Leffler, Ulf J. Nilsson, Anders Pedersen, Kristoffer Peterson, James A. Roper, Hans Schambye, Robert J. Slack, Susan Tantawi |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Journal of medicinal chemistry. 65(19) |
| ISSN: |
1520-4804 |
| Popis: |
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 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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