On May 31, 2020, Botros, Liza; Pronk, Manon C. A.; Juschten, Jenny; Liddle, John; Morsing, Sofia K. H.; van Buul, Jaap D.; Bates, Robert H.; Tuinman, Pieter R.; van Bezu, Jan S. M.; Huveneers, Stephan; Bogaard, Harm Jan; van Hinsbergh, Victor W. M.; Hordijk, Peter L.; Aman, Jurjan published an article.COA of Formula: C26H29Cl2N5O3 The title of the article was Bosutinib prevents vascular leakage by reducing focal adhesion turnover and reinforcing junctional integrity. And the article contained the following:
Endothelial barrier dysfunction leads to edema and vascular leak, causing high morbidity and mortality. Previously, Abl kinase inhibition has been shown to protect against vascular leak. Using the distinct inhibitory profiles of clin. available Abl kinase inhibitors, we aimed to provide a mechanistic basis for novel treatment strategies against vascular leakage syndromes. We found that the inhibitor bosutinib most potently protected against inflammation-induced endothelial barrier disruption. In vivo, bosutinib prevented lipopolysaccharide (LPS)-induced alveolar protein extravasation in an acute lung injury mice model. Mechanistically, mitogen-activated protein 4 kinase 4 (MAP4K4) was identified as important novel mediator of endothelial permeability, which signaled via ezrin, radixin and moesin proteins to increase turnover of integrin-based focal adhesions. The combined inhibition of MAP4K4 and Abl-related gene (Arg, also known as ABL2) by bosutinib preserved adherens junction integrity and reduced turnover of focal adhesions, which synergistically act to stabilize the endothelial barrier during inflammation. We conclude that MAP4K4 is an important regulator of endothelial barrier integrity, increasing focal adhesion turnover and disruption of cell-cell junctions during inflammation. Because it inhibits both Arg and MAP4K4, use of the clin. available drug bosutinib might form a viable strategy against vascular leakage syndromes. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).COA of Formula: C26H29Cl2N5O3
The Article related to bosutinib antiinflammatory agent focal adhesion acute lung injury, bosutinib, endothelial barrier function, focal adhesion, map4k4, tyrosine kinase inhibitors, vascular permeability and other aspects.COA of Formula: C26H29Cl2N5O3
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