| Autor: |
Marro, Martin L., Patterson, Andrew W., Lee, Lac, Deng, Lin, Reynolds, Aimee, Ren, Xianglin, Axford, Laura, Patnaik, Anup, Hollis-Symynkywicz, Micah, Casson, Nigel, Custeau, Dominique, Ames, Lisa, Loi, Sally, Zhang, Lihe, Honda, Toshiyuki, Blank, Jutta, Harrison, Tyler J., Papillon, Julien P.N., Hamann, Lawrence G., Marcinkeviciene, Jovita, Regard, Jean B. |
| Zdroj: |
The Journal of Pharmacology and Experimental Therapeutics; October 2018, Vol. 367 Issue: 1 p147-154, 8p |
| Abstrakt: |
Myeloperoxidase (MPO) is a leukocyte-derived redox enzyme that has been linked to oxidative stress and damage in many inflammatory states, including cardiovascular disease. We have discovered aminopyridines that are potent mechanism-based inhibitors of MPO, with significant selectivity over the closely related thyroid peroxidase. 1-((6-Aminopyridin-3-yl)methyl)-3-(4-bromophenyl)urea (Aminopyridine 2) inhibited MPO in human plasma and blocked MPO-dependent vasomotor dysfunction ex vivo in rat aortic rings. Aminopyridine 2 also showed high oral bioavailability and inhibited MPO activity in vivo in a mouse model of peritonitis. Aminopyridine 2 could effectively be administered as a food admixture, making it an important tool for assessing the relative importance of MPO in preclinical models of chronic inflammatory disease. |
| Databáze: |
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