马西替坦作用机制 - Medchemexpress - MCE中国

1、Product Data SheetMacitentanCat. No.: HY-14184CAS No.: 441798-33-0分式: CHBrNOS分量: 588.27作靶点: Endothelin Receptor; Apoptosis作通路: GPCR/G Protein; Apoptosis储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (84.99 mM)* means soluble, but saturation unknown.So

2、lventMass1 mg 5 mg 10 mgConcentration制备储备液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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶

3、解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.25 mM); Clear solution此案可获得 2.5 mg/mL (4.25 mM，饱和度未知) 的澄清溶液。以 1 mL

4、 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.25 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (4.25 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL

5、 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Macitentan (ACT-064992)化和肺动脉压的潜。有服活性，多肽 ETA 和 ETB (内素受体)双拮抗剂。Macitentan 有于特发性肺纤维IC & Target ETA/ETB1体外研究 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.体内研究 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.户使本产品发表的科研献 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: