冬凌草甲素作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetOridoninCat. No.: HY-N0004CAS No.: 28957-04-2分式: CHO分量: 364.43作靶點(diǎn): Akt; Bacterial作通路: PI3K/Akt/mTOR; Anti-infection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 : 150 mg/mL (411.60 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 m

2、g 10 mgConcentration制備儲(chǔ)備液1 mM 2.7440 mL 13.7201 mL 27.4401 mL5 mM 0.5488 mL 2.7440 mL 5.4880 mL10 mM 0.2744 mL 1.3720 mL 2.7440 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

3、 Vitro 式配制澄清的儲(chǔ)備液，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: 2.67 mg/mL (7.33 mM); Clear solution此案可獲得 2.67 mg/mL (7.33 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L

4、26.7 mg/mL 的澄 DMSO 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: 2.67 mg/mL (7.33 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.67 mg/mL (7.33 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 26.7 mg/mL 的澄 DMSO 儲(chǔ)備液加到 90

5、0 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.67 mg/mL (7.33 mM); Clear solution此案可獲得 2.67 mg/mL (7.33 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 26.7 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Oridonin (NSC-250682)從 Rabdosia rubescens 中得到的萜，為

6、 AKT 抑制劑，對(duì) AKT1 和 AKT2 的 IC50 值分別為8.4 和 8.9 M；Oridonin 具有抗腫瘤、抗菌、抗炎等功效。IC & Target Akt1 Akt28.4 M (IC50) 8.9 M (IC50)體外研究 Oridonin is an ATP-competitive inhibitor of AKT with IC50s of 8.4 and 8.9 M for AKT1 and AKT2, respectively.Oridonin (5, 10 or 20 M) obviously inhibits the growth of KYSE70, KYSE4

7、10 and KYSE450 ESCC cells via targetingAKT1/2. Oridonin (10 or 20 M) causes G2/M phase cell cycle arrest in KYSE70, KYSE410 and KYSE450 cells, andinduces apoptosis in these three cell lines at 20 M. In addition, Oridonin (5, 10 or 20 M) in combination withcisplatin or 5-FU enhances the inhibition of

8、 esophageal squamous cell carcinoma (ESCC) cell growth1. Oridonin (0.1and 1 M) preferentially suppresses AKT/mTOR signaling. Oridonin (1 M) also selectively suppresses growth ofbreast cancer cells with hyperactivation of AKT signaling2.體內(nèi)研究 Oridonin (160 mg/kg, p.o.) shows significant reduction in t

9、he tumor growth without obvious weigh loss in SCID mice bearing EG9 and HEG18 tumor cells. Oridonin treatment also suppresses the expression of Ki-67, phosphorylated AKT, GSK-3 or mTOR in mice1. Oridonin (15 mg/kg, i.p.) impairs cell growth in breast cancer with hyperactivation ofAKT signaling in nu

10、de mice2.PROTOCOLKinase Assay 1 For the AKT kinase assay, the ADP-Glo Kinase Assay Kit is used. Active AKT1 or AKT2 kinase and inactive GSK-3 assubstrate are mixed by 1 reaction buffer and then added to a white 96-well plate. Pure ATP provided in the kit isserially diluted obtain a final concentrati

11、on of 0, 1, 10, 50, and 100 M. GSK-3 is added to reach a finalconcentration of 2.5, 5, 10 or 20 M and DMSO is used as a control. The mixed solution is incubated at roomtemperature and luciferase activity is measured using the Luminoskan Ascent plate reader1.MCE has not independently confirmed the ac

12、curacy of these methods. They are for reference only.Cell Assay 1 Cells are seeded (6103 cells/well for KYSE70; 2.5103 cells/well for KYSE410; 2103 cells/well for KYSE450) in 96-well plates and incubated for 24 h and then treated with different amounts of Oridonin or vehicle. After incubationfor 24,

13、 48 or 72 h, cell proliferation is measured by the MTT assay. For anchorage-independent cell growthassessment, cells (2.5, 5 or 10 M Oridonin) suspended in complete medium are added to 0.3% agar with vehicle,2.5, 5 or 10 M Oridonin in a top layer over a base layer of 0.5% agar with vehicle, 2.5, 5 o

14、r 10 M Oridonin. Thecultures are maintained at 37C in a 5% CO2 incubator for 3 weeks and then colonies are visualized under amicroscope and counted using the Image-Pro Plus software program1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 ww

15、w.MedChemEAnimal Mice2Administration 2 Breast cancer cells are harvested and resuspended in 40% Matrigel-Basement Membrane Matrix, LDEV-free, and then injected (100 L per site) into the fourth pair of mammary fat pads of nude mice (CrTac: NCr-Foxn1nu). Tumors aremeasured in two dimensions using manu

16、al calipers. Tumor volume is calculated using the formula: Volume = 0.5 length width width. Tumor volume is measured every 2-3 days. Upon harvesting, tumors are fixed in formalinovernight and then in 70% ethanol for histopathology analysis. Mice are treated with Oridonin (15 mg/kg) in 1%Pluronic F68

17、 or vehicle (1% Pluronic F68) daily by intraperitoneal (IP) injection. BEZ235 is reconstituted 1:9 in 1-methyl-2 pyrolidone and polyethylene glycol 300 (PEG300) Mice are treated with this compound formulation at 45mg/kg daily (QD) by oral gavage2.MCE has not independently confirmed the accuracy of t

18、hese methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Biochem Pharmacol. 2020 Apr 27:113998.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Song M, et al. Targeting AKT with oridonin inhibits growth of esophageal squamous cell carcinoma in vitro and patient derived xenografts in vivo. MolCancer Ther. 2018 Apr 25. pii: molcanther.0823.2017.2. Sun B, et al. Oridonin inhibits aberrant AKT activation i