Stem cell mobilizers targeting chemokine receptor CXCR4: renoprotective application in acute kidney injury
| Autor: | Chung-Yu Huang, Jiing-Jyh Jan, Min-Hsien Wang, Szu-Huei Wu, Ming-Chen Chou, Kak-Shan Shia, Amit A. Sadani, Chen-Tso Tseng, Ying-Chieh Wong, Ching-Fang Yeh, Lun K. Tsou, Jen-Shin Song, Kai-Chia Yeh, Chia-Yi Cheng, Chien-Huang Wu, Chun-Ping Chang, Kuei-Hua Chang, Chiung-Tong Chen |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Receptors CXCR4 Pharmacology CXCR4 Mice Drug Discovery medicine Animals Humans Progenitor cell Blood urea nitrogen Hematopoietic Stem Cell Mobilization Chemistry Chemotaxis Acute kidney injury Acute Kidney Injury Triazoles medicine.disease Flow Cytometry Hematopoietic Stem Cells Rats Mice Inbred C57BL Haematopoiesis Reperfusion Injury Immunology Quinazolines Molecular Medicine Stem cell Adult stem cell Signal Transduction |
| Zdroj: | Journal of medicinal chemistry. 58(5) |
| ISSN: | 1520-4804 |
| Popis: | We have discovered a novel series of quinazoline-based CXCR4 antagonists. Of these, compound 19 mobilized CXCR4(+) cell types, including hematopoietic stem cells and endothelial progenitor cells, more efficiently than the marketed 1 (AMD3100) with subcutaneous administration at the same dose (6 mg/kg) in mice. This series of compounds thus provides a set of valuable tools to study diseases mediated by the CXCR4/SDF-1 axis, including myocardial infarction, ischemic stroke, and cancer metastasis. More importantly, treatment with compound 19 significantly lowered levels of blood urea nitrogen and serum creatinine in rats with renal ischemia-reperfusion injury, providing evidence for its therapeutic potential in preventing ischemic acute kidney injury. CXCR4 antagonists such as 19 might also be useful to increase circulating levels of adult stem cells, thereby exerting beneficial effects on damaged and/or inflamed tissues in diseases that currently are not treated by standard approaches. |
| Databáze: | OpenAIRE |
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