馬西替坦作用機制 - Medchemexpress - MCE中國

1、Product Data SheetMacitentanCat. No.: HY-14184CAS No.: 441798-33-0分式: CHBrNOS分量: 588.27作靶點: Endothelin Receptor; Apoptosis作通路: GPCR/G Protein; Apoptosis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 (84.99 mM)* means soluble, but saturation unknown.So

2、lventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.6999 mL 8.4995 mL 16.9990 mL5 mM 0.3400 mL 1.6999 mL 3.3998 mL10 mM 0.1700 mL 0.8499 mL 1.6999 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜?/p>

3、解案。以下溶解案都請先按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.25 mM); Clear solution此案可獲得 2.5 mg/mL (4.25 mM，飽和度未知) 的澄清溶液。以 1 mL

4、 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.25 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (4.25 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL

5、 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Macitentan (ACT-064992)化和肺動脈壓的潛。有服活性，多肽 ETA 和 ETB (內(nèi)素受體)雙拮抗劑。Macitentan 有于特發(fā)性肺纖維IC & Target ETA/ETB1體外研究 Tube formation ability is restored when microvascular endothelial cells are preincubated with BOS or macitentan(ACT-064992), also reducing the

6、expression of mesenchymal markers and restoring CD31 expression and theimbalance between VEGF-A and VEGF-A165b1. Macitentan inhibits OATP1B1-mediated uptake of atorvastatin andOATP1B3-mediated uptake of estrone-3-sulfate with IC50 SE values of 6.3 0.7 and 11.8 5.0 M, respectively3.Treatment with mac

7、itentan or with ACT-132577 does not lead to intracellular accumulation of R123 in HeyA8-MDR,showing that these compounds are not P-gp inhibitors4.體內(nèi)研究 Macitentan (ACT-064992; 25 mg/kg/day, p.o.) prevents increased production of vasoactive and fibrogenic factors, NF-B activation, structural and funct

8、ional changes, and increases extracellular matrix protein production in type 2diabetes in type 2 diabetes2. Macitentan (10 mg/kg, p.o.) coupled with once-per-week 5 mg/kg taxol, significantlyreduces the weight (size) of HeyA8-MDR tumors in mice. Combination therapy with macitentan (10 or 50 mg/kg, b

9、utnot 5 mg/kg) and taxol or macitentan (10 mg/kg) and cisplatinum significantly reduces the number of proliferatingKi-67-positive cells4.PROTOCOLAnimal Male db/db mice and age and sex-matched controls (27-32 g) are used for the assay. RandomLy selected diabeticAdministration 2 animals are monitored

10、for either 2 months or for 4 months after onset of diabetes. Groups (n=7/group) of thediabetic mice are subjected to oral macitentan treatment for the same period (25 mg/kg/day, food admix). Theanimals are monitored through assessment of body weight and blood glucose.MCE has not independently confir

11、med the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 BMC Cancer. 2018 Feb 6;18(1):154. Comp Biochem Physiol A Mol Integr Physiol. 2019 Nov 23:110620. Journal of Pharmaceutical Quality Assurance. 18 June 2015.See more customer validations on HYPERLINK www.MedChemE www.MedChemERE

12、FERENCES1. Corallo C, et al. Bosentan and macitentan prevent the endothelial-to-mesenchymal transition (EndoMT) in systemic sclerosis: in vitro study. Arthritis ResTher. 2016 Oct 6;18(1):228.Page 2 of 3 www.MedChemE2. Sen S, et al. Renal, retinal and cardiac changes in type 2 diabetes are attenuated

13、 by macitentan, a dual endothelin receptor antagonist. Life Sci. 2012 Apr13.3. Bruderer S, et al. Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist.AAPS J. 2012 Mar;14(1):68-78.4. Kim SJ, et al. Antivascular therapy for multidrug-resistant ovarian tumors by macitentan, a dual endothelin receptor antagonist.Transl Oncol. 2012Feb;5(1):39-47.McePdfHeightCaution: