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

2、tion制備儲(chǔ)備液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請(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液

3、，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)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(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.01 mM); Clear solution此案可獲得 2.5 mg/mL (7.01 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO

4、 儲(chǔ)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(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.01 mM); Clear solution此案可獲得 2.5 mg/mL (7.01 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理

5、鹽溶液中，混合BIOLOGICAL ACTIVITY物活性 Sulindac (MK-231)種甾體類抗炎劑，能夠抑制 COX-2 的活性，同時(shí)可抑制 COX-2 的過表達(dá)。IC & Target COX-2 Autophagy體外研究 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.體內(nèi)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