魚藤素作用機制 - Medchemexpress - MCE中國

1、Product Data SheetDeguelinCat. No.: HY-13425CAS No.: 522-17-8分式: CHO分量: 394.42作靶點: Akt; Autophagy作通路: PI3K/Akt/mTOR; Autophagy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 (126.77 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10

2、 mgConcentration制備儲備液1 mM 2.5354 mL 12.6768 mL 25.3537 mL5 mM 0.5071 mL 2.5354 mL 5.0707 mL10 mM 0.2535 mL 1.2677 mL 2.5354 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(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vit

3、ro 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(dāng)保存；體內(nèi)實驗的作液，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. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.34 mM); Clear solution此案可獲得 2.5 mg/mL (6.34 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 m

4、g/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% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.34 mM); Suspended solution; Need ultrasonicPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (6.34 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L 25.0 mg

5、/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.34 mM); Clear solution此案可獲得 2.5 mg/mL (6.34 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 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Deguelin種天然存在的類胡蘿素， 種有效的 PI3K/A

6、KT 抑制劑。IC & Target Akt體外研究 Deguelin (0-500 nM) in a dose and time dependent manner inhibits the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin at all concentrations fails to reduce cell numbers in the presence of 1 ng EGF but in thepresence of EGF 20 ng reinstated deguelin mediat

7、ed growth inhibition. Deguelin treated cells show reducedexpression of Survivin as determined by western blot and immunofluorescence examinations. Deguelin inhibits p-ERKand its downstream target p-STAT-3 and c-Myc expression in a dose dependent manner1. Deguelin down-regulatesAkt signaling probably

8、 by disrupting its association with Hsp 90 in cultured HNSCC cells. Deguelin deguelin disruptsthe association between Hsp 90 with survivin and Cdk4. Deguelin deguelin treatment increases cellular ceramide levelthrough de novo synthase pathway to mediate HNSCC cell death and apoptosis2. Deguelin inhi

9、bits the proliferationof MPC-11 cells in a concentration- and time-dependent manner and causes the apoptotic death of MPC-11 cells.Following exposure to deguelin, the phosphorylation of Akt is decreased. Deguelin-induced apoptosis ischaracterized by the upregulation of Bax, downregulation of Bcl-2 a

10、nd activation of caspase-33.體內(nèi)研究 Deguelin (2 or 4 mg/kg, i.p.) reduces the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously inathymic mice1. Deguelin (4 mg/kg, p.o.) treatment shows a great inhibition in tumor growth, which is demonstratedby reduced tumor size and improved mice s

11、urvival and, indicating a significant anti-tumor ability by deguelin in vivo2. In the colon cancer xenograft model, the volume of the tumor treated with deguelin is significantly lower than thatof the control, and the apoptotic index for deguelin-treated mice is much higher4.PROTOCOLKinase Assay 2 C

12、aspase 3 activity is determined using Caspase-Glo-3 assays. This assay provides luminogenic substrate in a buffersystem optimized for each specific caspase activity. The caspase cleavage of the substrate is followed by generationof a luminescent signal. The signal generated is proportional to the am

13、ount of caspase activity present in the sample.Protein (10 g) from the cell samples is diluted in water to a final volume of 50 L and added to a white 96-wellmicrotitre plate, followed by 50 L of Caspase-Glo-3 reagent. The plate is sealed and gently mixed at 300-500 rpmfor 30 s and incubated at room

14、 temperature for 30 min. Luminescence is measured in a microplate reader (TECANInfinite 200).MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Breast cancer cells are incubated with increasing concentration of Deguelin ranging from 31 nM to 5

15、00 nM for 24, 48and 72 h. At the termination the cells are trypsinized and cell proliferation is evaluated by counting cells using Z-series Coulter counter. Data are presented as MeanSE percent of control.MCE has not independently confirmed the accuracy of these methods. They are for reference only.

16、Page 2 of 3 www.MedChemEAnimal Six to seven weeks old female athymic mice (nu/nu) are housed in a barrier free environment under 242CAdministration 1 temperature, 5010% relative humidity, and 12-hour light/12-hour dark cycle. Mice are provided with sterile mousechow and water ad libitum. MDA-MB-231

17、cells (3.0 million cells/animal) are suspended in sterile PBS and theninjected subcutaneously into the dorsal flank region using 23 g hypodermic needle. Animals are observed daily forthe growth of palpable tumor at the site of injection. Once the tumor (approximately 50 mm3) appears, the mice areran

18、domized in to three groups, animals receiving either 1) vehicle as a control 2) Deguelin treatment at 2 mg/kgbodyweight dose or 3) Deguelin at 4 mg/kg body weight. Each group consists of 10 animals. Vehicle or Deguelin isadministered through i.p. injection daily for 21 days. Animals are monitored da

19、ily for the signs of drug/vehicleassociated toxicity and weighed once weekly. Growth of tumor at the site of cell injection is monitored everyalternate day and of tumor size is measured using calipers. Tumor volume is calculated by using the well-establishedformula: tumor volume (mm3)=/6 lengthwidth

20、depth. Data represent the mean tumor volume+SE (mm3) in eachgroup. The animals are sacrificed at the indicated time unless they appear to be moribund or tumors show sign ofnecrosis. At termination, the tumor is excised, freed from connective tissue and other organs, a small piece is fixed in10% buff

21、ered formalin and remaining tumor is snap frozen for future biochemical analysis. Liver, lung, kidney andspleen are excised and weighed.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Int J Mol Med. 2018 Jun;41(6):3157-3166.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Mehta R, et al. Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells. PLoS One. 2013 Jun 10;8(6):e65113.2.