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1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMethylthiouracilCat. No.: HY-B0513CAS No.: 56-04-2Synonyms: MTU分式: CHNOS分量: 142.18作靶点: NF-B; TNF Receptor; Interleukin Related; ERK作通路: NF-B; Apoptosis; Immunology/Inflammation; MAPK/ERKPathway; Stem Cell/Wnt储存式: Powder -20C 3 y
2、ears4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (351.67 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (17.58 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE2. 请依序添加每种溶剂: 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (17.58 mM); Clear so
3、lutionBIOLOGICAL ACTIVITY物活性 Methylthiouracil种抗甲状腺剂。Methylthiouracil 抑制 TNF- 和 IL-6 的产以及 NF-B 和 ERK1/2 的活化。IC50 & Target NF-B TNF- IL-6 ERK1ERK2体外研究 HUVECs are treated with various concentrations of MTU (0-20 M) for 6 h after the addition of LPS (100ng/mL) for 4 h. MTU inhibits LPS-mediated hyperper
4、meability in endothelial cells, with the optimal effectoccurring at a concentration above 5 M. The effects of MTU are examined on HUVEC actin cytoskeletalarrangement by immunofluorescence staining of HUVEC monolayers with F-actin labeled fluoresceinphalloidin. Control HUVECs exhibit a random distrib
5、ution of F-actin throughout the cells, with somelocalization of actin filament bundles at the cell boundaries. Barrier disruption by LPS (100 ng/mL) ismanifested by the formation of paracellular gaps in HUVECs. In addition, post-treatment with MTU (10 or 20M) results in inhibited formation of LPS-in
6、duced paracellular gaps with the formation of dense F-actin rings.To test the cytotoxicity of MTU, cellular viability assays are performed in HUVECs treated with MTU for 24 h.At concentrations up to 20 M, MTU does not affect cell viability 1.体内研究 MTU treatment results in marked inhibition of the per
7、itoneal leakage of dye induced by LPS. The averagecirculating blood volume for mice is 72 mL/kg. Because the average mouse weight in this study is 27 g, andthe average blood volume is 2 mL, the injected MTU (142 or 284 g/kg) results in a maximum concentrationof 10 or 20 M in the peripheral blood 1.P
8、ROTOCOLCell Assay 1 MTT is used as an indicator of cell viability. Primary human umbilical vein endothelial cells (HUVECs) aregrown in 96-well plates at a density of 5103 cells/well. After 24 h, the cells are washed with fresh mediumand treated with MTU (0-20 M). After a 48 h incubation period, the
9、cells are washed, and 100 L of MTT (1mg/mL) is added, followed by incubation for 4 h. Finally, DMSO (150 L) is added to solubilize the formazansalt formed, and the amount of formazan salt is determined by measuring the OD at 540 nm using amicroplate reader 1.MCE has not independently confirmed the a
10、ccuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Male C57BL/6 mice (6-7 weeks old; average weight, 27 g) are used in this study. Mice are administered LPS(0.3 mg/mouse or 15 mg/kg, intravenously). After 4 h, the mice are intravenously treated with MTU (142 or284 g/
11、kg, for 6 h) and injected with 1% Evans blue dye solution in normal saline. Six hours later, the mice2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEare sacrificed and peritoneal exudates are collected by washing cavities with 5 mL of normal saline and bycentrifuging at 200 g for 10 min. The absorb
12、ance of the supernatant is read at 650 nm. Vascularpermeabilities are expressed as g of dye/mouse that leaked into the peritoneal cavity and are determinedusing a standard curve.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Ku SK, et al. Anti-inflammatory effects of methylthiouracil in vitro and in vivo. Toxicol Appl Pharmacol. 2015 Nov 1;288(3):374-86.McePdfHeightCaut
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