1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMD2-IN-1Cat. No.: HY-103483CAS No.: 111797-22-9分式: CHO分量: 358.39作靶點: Toll-like Receptor (TLR)作通路: Immunology/Inflammation儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (139.51 mM;

2、 Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 3.25 mg/mL (9.07 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3.25 mg/mL (9.07 mM); Suspended solution; Need ultrasonic3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.Me

3、dChemESolubility: 3.25 mg/mL (9.07 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 MD2-IN-1髓樣分化蛋 2 (MD2) 的抑制劑，對重 組 MD2 (rhMD2) 的 KD 值為 189 M。IC50 & Target KD: 189 M (rhMD2) 1體外研究 Myeloid differentiation protein 2 (MD2) is a co-receptor of TLR4. Among those derivatives, MD2-IN-1(compound 20) shows the stro

4、ngest inhibitory effect on LPS-induced expression of both TNF- and IL-6.Compare to the vehicle, LPS alone largely increases the amount of TLR4/MD2 complex, while pretreatmentwith MD2-IN-1 inhibits the increase of TLR4/MD2 complex to the vehicle level. SPR analysis shows thatMD2-IN-1 exhibits recogni

5、zable binding to rhMD2 protein in a dose-dependent manner, with a KD value of189M, while the KD value of xanthohumol binding to MD2 is 460M. Pre-treatment with different doses ofMD2-IN-1 dose-dependently reduces FITC-LPS binding to MD2 in cell surface membranes, with a 65%inhibition at 10M in terms

6、of mean fluorescence intensity. Pretreatment with MD2-IN-1 also dose-dependently blocks LPS-induced MAPK phosphorylation in the MPMs 1.體內研究 Administration of MD2-IN-1 evidently reduces the LPS-induced increase in protein concentrations in BALF.The lung wet/dry weight ratio is markedly higher in the

7、LPS-treated group than the control group, and MD2-IN-1 treatment reduces LPS-induced pulmonary edema. LPS also causes observable lung histopathologicchanges, including areas of inflammatory infiltration, hemorrhage, interstitial edema, thickening of thealveolar wall, and lung tissue destruction. The

8、se histopathological changes are ameliorated in the MD2-IN-1treatment group 1.PROTOCOLCell Assay 1 Mouse RAW264.7 macrophages are starved for 3h before experimentation. Cells are incubated with orwithout FITC-LPS (50g/mL) in the presence or absence of MD2-IN-1 (0.1, 1 and 10M) for 30min. Afterincuba

9、tion, macrophages are fixed with paraformaldehyde for 10min at 4C and washed with PBS beforebeing analyzed by flow cytometry 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male Sprague Dawley (SD) rats are randomly divided into three groups, d

10、esignated “control” (5 rats, onlyAdministration 1 receive the vehicle of 0.9% saline), “LPS” (7 rats, receive 5mg/kg LPS alone) and “MD2-IN-1 (20)+LPS” (6rats, receive both MD2-IN-1 and 5mg/kg LPS). Prior to LPS-induced Acute lung injury (ALI), the MD2-IN-1+LPS group rats are treated intragastricall

11、y with MD2-IN-1 at a dosage of 20mg/kg/day continuously for oneweek. Under ether anesthesia, all the rats are exposed their trachea and challenged with intratrachealinstillation of 50L of LPS, while the control group challenged with intratracheal instillation of 50L of 0.9%saline. Rats are then euth

12、anized with ketamine after 6h of LPS induction 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Zhang Y, et al. Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury.Sci Rep. 2016 Apr 27;6:25130.McePdfHeightCautio