1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOridoninCat. No.: HY-N0004CAS No.: 28957-04-2Synonyms: NSC-250682; Isodonol分式: CHO分量: 364.43作靶點: Akt作通路: PI3K/Akt/mTOR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 : 150 mg/mL (411.60 mM)*

2、means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液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，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作

3、液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.67 mg/mL (7.33 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.67 mg/mL (7.33 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師ww

4、w.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.67 mg/mL (7.33 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Oridonin (NSC-250682)從 Rabdosia rubescens 中得到的萜，為 AKT 抑制劑，對 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。IC50 & Target Akt1 Akt28.4 M (IC50) 8.9 M (IC50)體外研究 Oridonin is

5、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, KYSE410 and KYSE450ESCC cells via targeting AKT1/2. Oridonin (10 or 20 M) causes G2/M phase cell cycle arrest in KYSE70,KYSE410 and KYSE45

6、0 cells, and induces apoptosis in these three cell lines at 20 M. In addition, Oridonin(5, 10 or 20 M) in combination with cisplatin or 5-FU enhances the inhibition of esophageal squamous cellcarcinoma (ESCC) cell growth 1. Oridonin (0.1 and 1 M) preferentially suppresses AKT/mTOR signaling.Oridonin

7、 (1 M) also selectively suppresses growth of breast cancer cells with hyperactivation of AKTsignaling 2.體內(nèi)研究 Oridonin (160 mg/kg, p.o.) shows significant reduction in the tumor growth without obvious weigh loss inSCID mice bearing EG9 and HEG18 tumor cells. Oridonin treatment also suppresses the exp

8、ression of Ki-67, phosphorylated AKT, GSK-3 or mTOR in mice 1. Oridonin (15 mg/kg, i.p.) impairs cell growth in breastcancer with hyperactivation of AKT signaling in nude mice 2.PROTOCOLKinase Assay 1 For the AKT kinase assay, the ADP-Glo Kinase Assay Kit is used. Active AKT1 or AKT2 kinase andinact

9、ive GSK-3 as substrate are mixed by 1 reaction buffer and then added to a white 96-well plate. PureATP provided in the kit is serially diluted obtain a final concentration of 0, 1, 10, 50, and 100 M. GSK-3 isadded to reach a final concentration of 2.5, 5, 10 or 20 M and DMSO is used as a control. Th

10、e mixedsolution is incubated at room temperature and luciferase activity is measured using the Luminoskan Ascentplate reader 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cells are seeded (6103 cells/well for KYSE70; 2.5103 cells/well f

11、or KYSE410; 2103 cells/well forKYSE450) in 96-well plates and incubated for 24 h and then treated with different amounts of Oridonin orvehicle. After incubation for 24, 48 or 72 h, cell proliferation is measured by the MTT assay. For anchorage-independent cell growth assessment, cells (2.5, 5 or 10

12、M Oridonin) suspended in complete medium areadded 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 withvehicle, 2.5, 5 or 10 M Oridonin. The cultures are maintained at 37C in a 5% CO2 incubator for 3 weeksand then colonies are visualized under a micros

13、cope and counted using the Image-Pro Plus software2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEprogram 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Breast cancer cells are harvested and resuspended in 40% Matrigel-

14、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 are measured in two dimensions using manual calipers. Tumor volume is calculated usingthe formula: Volume = 0.5 length width width. Tumor volume

15、is measured every 2-3 days. Uponharvesting, tumors are fixed in formalin overnight and then in 70% ethanol for histopathology analysis. Miceare treated with Oridonin (15 mg/kg) in 1% Pluronic F68 or vehicle (1% Pluronic F68) daily by intraperitoneal(IP) injection. BEZ235 is reconstituted 1:9 in 1-me

16、thyl-2 pyrolidone and polyethylene glycol 300 (PEG300)Mice are treated with this compound formulation at 45 mg/kg daily (QD) by oral gavage 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Song M, et al. Targeting AKT with oridonin inhibits growth of esophageal squamous cell carcinoma in vitro and patient derivedxenografts in vivo. Mol Cancer Ther. 2018 Apr 25. pii: molcanther.0823.2017.2. Sun B, et al. Oridonin inhibits aberrant AKT activation in brea