舒林酸作用机制 - Medchemexpress - MCE中国

1、Product Data SheetSulindacCat. No.: HY-B0008CAS No.: 38194-50-2分式: CHFOS分量: 356.41作靶点: COX; Autophagy作通路: Immunology/Inflammation; Autophagy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 : 100 mg/mL (280.58 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentra

2、tion制备储备液1 mM 2.8058 mL 14.0288 mL 28.0576 mL5 mM 0.5612 mL 2.8058 mL 5.6115 mL10 mM 0.2806 mL 1.4029 mL 2.8058 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解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液

3、，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 (7.01 mM); Clear solution此案可获得 2.5 mg/mL (7.01 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO

4、 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% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.01 mM); Clear solution此案可获得 2.5 mg/mL (7.01 mM，饱和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄均匀。DMSO 储备液加到 900 L 20% 的 SBE-CD 理

5、盐溶液中，混合BIOLOGICAL ACTIVITY物活性 Sulindac (MK-231)种甾体类抗炎剂，能够抑制 COX-2 的活性，同时可抑制 COX-2 的过表达。IC & Target COX-2 Autophagy体外研究 Sulindac (MK-231) is a non-steroidal antiinflammatory agent, acts as a COX-2 inhibitor, and inhibits overexpression ofCOX-21. Sulindac (MK-231) (0.1 mM to 0.5 mM) causes limited dea

6、th in both p53 wt and p53 null HCT116 cells, butin combination with vitamin C, it dramatically increases almost 5-fold in cell death in p53 wt HCT116 cells relative tothe vitamin C alone, and such an effect is involving caspase activation and p53 function in these cells, and via ROS-mediated pathway

7、. Sulindac combined with vitamin C significantly increases PUMA levels, but shows no effect onBim, Bcl-2 and Mcl-1 levels2. Sulindac (MK-231) (500 M) in combination with celecoxib blocks transforming growthfactor (TGF)-1-induced epithelial-mesenchymal transition, migration and invasion in A549 cells

8、. The combinationalso suppresses involvement of sirtuin 1 (SIRT1) in transforming growth factor (TGF)-1-induced epithelial-mesenchymal transition (EMT)3.体内研究 Sulindac (MK-231) (0.5 0.1 mg/day) decreases COX, modolates PGE2 levels and prevents tumor formation in theMin mice1.PROTOCOLCell Assay 2 Cell

9、s are treated with Sulindac (MK-231) and/or vitamin C at the indicated doses for 48 h, and cell viability isanalyzed using a trypan blue exclusion assay. For the annexin V staining assay, cells are treated with 0.5 mM Sulindac(MK-231) and/or 0.5 mM vitamin C for 48 h. The cells are then trypsinized,

10、 washed with PBS, stained with propidiumiodide (PI) and FITC-labeled annexin V for 30 min, and analyzed by flow cytometry using a fluorescence-activated cellsorter2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice1Administration 1 Female C57B

11、L16J-Min/+ (Min) mice at 5 weeks of age are used in the assay. Beginning at 5-6 weeks of age, 10 Min mice are fed a low-fat AIN-76A chow diet modified with 0.001% ethoxyquin and Sulindac (MK-231), 0.5 0.1mg/day (0.05 mg/kcal/day or approximately 160 ppm) in drinking water. As controls, 9 Min mice an

12、d 5 C57BL/6J-+/+non-affected littermates (+/+) are fed AIN-76A diet without Sulindac. Animals are checked daily for signs of distressor anemia. Animals and their food are weighed twice weekly. During the course of the experiment, there is nodifference in body weight or food consumption among the var

13、ious study groups. No toxicity is observed in theMin/Sulindac group. At 110 days of age, all mice are euthanized by CO2 inhalation, and their intestinal tracts areremoved from esophagus to distal rectum, opened, flushed with saline, and examined under 3 magnification toobtain tumor counts. Tumors ar

14、e counted by an individual blinded to the animals genetic status and treatment.Multiple samples of grossly normal, full-thickness bowel are harvested from the mid small intestine and either frozenin liquid nitrogen or fixed in 10% formalin for histological examination. All samples used for the analy

15、ses in this studyare taken from mid small intestine1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemEREFERENCES1. Boolbol SK, et al. Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of

16、 familial adenomatous polyposis.Cancer Res. 1996 Jun 1;56(11):2556-60.2. Gong EY, et al. Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells.Toxicol Lett. 2016 Sep 6;258:126-133.3. Cha BK, et al. Celecoxib and sulindac inhibit TGF-1-induced epithelial-mesenchymal transition and suppress lung cancer migration and invasion viadownregulation of sirtuin 1. Oncotarget. 201