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排序方式: 共有235条查询结果,搜索用时 15 毫秒
231.
Luping Pang Stephen D. Weeks Martin Juhs Sergei V. Strelkov Jan Zitko Arthur Van Aerschot 《International journal of molecular sciences》2021,22(15)
Human cytosolic prolyl-tRNA synthetase (HcProRS) catalyses the formation of the prolyl-tRNAPro, playing an important role in protein synthesis. Inhibition of HcProRS activity has been shown to have potential benefits in the treatment of fibrosis, autoimmune diseases and cancer. Recently, potent pyrazinamide-based inhibitors were identified by a high-throughput screening (HTS) method, but no further elaboration was reported. The pyrazinamide core is a bioactive fragment found in numerous clinically validated drugs and has been subjected to various modifications. Therefore, we applied a virtual screening protocol to our in-house library of pyrazinamide-containing small molecules, searching for potential novel HcProRS inhibitors. We identified a series of 3-benzylaminopyrazine-2-carboxamide derivatives as positive hits. Five of them were confirmed by a thermal shift assay (TSA) with the best compounds 3b and 3c showing EC50 values of 3.77 and 7.34 µM, respectively, in the presence of 1 mM of proline (Pro) and 3.45 µM enzyme concentration. Co-crystal structures of HcProRS in complex with these compounds and Pro confirmed the initial docking studies and show how the Pro facilitates binding of the ligands that compete with ATP substrate. Modelling 3b into other human class II aminoacyl-tRNA synthetases (aaRSs) indicated that the subtle differences in the ATP binding site of these enzymes likely contribute to its potential selective binding of HcProRS. Taken together, this study successfully identified novel HcProRS binders from our anti-tuberculosis in-house compound library, displaying opportunities for repurposing old drug candidates for new applications such as therapeutics in HcProRS-related diseases. 相似文献
232.
Kamenopoulou V van Dijk JW Ambrosi P Bolognese-Milsztajn T Castellani CM Currivan L Falk R Fantuzzi E Figel M Alves JG Ginjaume M Janzekovic H Kluszczynski D Lopez MA Luszik-Bhadra M Olko P Roed H Stadtmann H Vanhavere F Vartiainen E Wahl W Weeks A Wernli C 《Radiation protection dosimetry》2006,118(2):139-143
233.
234.
Payers are increasingly interested in knowing whether they are receiving value for the dollars they spend on health care. Because economic analysis will be used as a means of evaluating radiation therapy, it is important that radiation oncologists understand the basic methodology employed in such analyses. This review article describes the four basic types of economic analyses: cost minimization, cost effectiveness, cost utility, and cost benefit. Specification of alternative therapies, choice of perspective of the analysis, measurements of costs and benefits, and the role of discounting and sensitivity analyses are discussed. Published economic analyses that pertain directly to treatment with radiation therapy are reviewed. Finally, we close with a brief discussion of the potential areas for future economic outcomes research in radiation oncology. 相似文献
235.
Julie A Cakebread Michael P Agnew Michael G Weeks Marlon M Reis 《International Journal of Dairy Technology》2023,76(4):1012-1018
Assessment of milk fatty acids has been proposed to support farm management practices including adjustment of feeding regimes and monitoring animal status. This study assessed the performance of a miniaturised near infrared (NIR) sensor for assessment of fatty acids in milk. Samples (n = 483) were from 114 farms, varying in lactation stages within two production seasons and included different dairy breeds. The fatty acids (C4:0, C6:0, C14:0, C16:0, C18:1 c9, SFA, MUFA, SCFA, BCFA) showed Ratio of performance to deviation values higher than two. The performance was equivalent to other independent studies utilising NIR. However, in this study, we used a low-cost NIR spectrophotometer suitable for on-the-farm use. 相似文献