Deguelin-minus-Deguelin-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDeguelinCat. No.: HY-13425CAS No.: 522-17-8Synonyms: (-)-Deguelin; (-)-cis-Deguelin分式: CHO分量: 394.42作靶点: Akt作通路: PI3K/Akt/mTOR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 : 50 mg/mL (126.7

2、7 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.34 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.34 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90%

3、 corn oilSolubility: 2.5 mg/mL (6.34 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Deguelin种天然存在的类胡萝素， 种有效的 PI3K/AKT 抑制剂。IC50 & Target Akt体外研究 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 fai

4、ls to reduce cell numbers in the presence of 1ng EGF but in the presence of EGF 20 ng reinstated deguelin mediated growth inhibition. Deguelin treatedcells show reduced expression of Survivin as determined by western blot and immunofluorescenceexaminations. Deguelin inhibits p-ERK and its downstream

5、 target p-STAT-3 and c-Myc expression in a dosedependent manner 1. Deguelin down-regulates Akt signaling probably by disrupting its association with Hsp90 in cultured HNSCC cells. Deguelin deguelin disrupts the association between Hsp 90 with survivin andCdk4. Deguelin deguelin treatment increases c

6、ellular ceramide level through de novo synthase pathway tomediate HNSCC cell death and apoptosis 2. Deguelin inhibits the proliferation of MPC-11 cells in aconcentration- and time-dependent manner and causes the apoptotic death of MPC-11 cells. Followingexposure to deguelin, the phosphorylation of A

7、kt is decreased. Deguelin-induced apoptosis is characterizedby the upregulation of Bax, downregulation of Bcl-2 and activation of caspase-3 3.体内研究 Deguelin (2 or 4 mg/kg, i.p.) reduces the in vivo tumor growth of MDA-MB-231 cells transplantedsubcutaneously in athymic mice 1. Deguelin (4 mg/kg, p.o.)

8、 treatment shows a great inhibition in tumorgrowth, which is demonstrated by reduced tumor size and improved mice survival and, indicating a significantanti-tumor ability by deguelin in vivo 2. In the colon cancer xenograft model, the volume of the tumor treatedwith deguelin is significantly lower t

9、han that of the control, and the apoptotic index for deguelin-treated miceis much higher 4.PROTOCOLKinase Assay 2 Caspase 3 activity is determined using Caspase-Glo-3 assays. This assay provides luminogenic substrate ina buffer system optimized for each specific caspase activity. The caspase cleavag

10、e of the substrate isfollowed by generation of a luminescent signal. The signal generated is proportional to the amount ofcaspase activity present in the sample. Protein (10 g) from the cell samples is diluted in water to a finalvolume of 50 L and added to a white 96-well microtitre plate, followed

11、by 50 L of Caspase-Glo-3 reagent.The plate is sealed and gently mixed at 300-500 rpm for 30 s and incubated at room temperature for 30 min.Luminescence is measured in a microplate reader (TECAN Infinite 200).MCE has not independently confirmed the accuracy of these methods. They are for reference on

12、ly.Cell Assay 1 Breast cancer cells are incubated with increasing concentration of Deguelin ranging from 31 nM to 500 nMfor 24, 48 and 72 h. At the termination the cells are trypsinized and cell proliferation is evaluated by counting2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEcells using Z-seri

13、es 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.Animal Six to seven weeks old female athymic mice (nu/nu) are housed in a barrier free environment under 242CAdministration 1 temperature

14、, 5010% relative humidity, and 12-hour light/12-hour dark cycle. Mice are provided with sterilemouse chow and water ad libitum. MDA-MB-231 cells (3.0 million cells/animal) are suspended in sterile PBSand then injected subcutaneously into the dorsal flank region using 23 g hypodermic needle. Animals

15、areobserved daily for the growth of palpable tumor at the site of injection. Once the tumor (approximately 50mm3) appears, the mice are randomized in to three groups, animals receiving either 1) vehicle as a control 2)Deguelin treatment at 2 mg/kg bodyweight dose or 3) Deguelin at 4 mg/kg body weigh

16、t. Each group consistsof 10 animals. Vehicle or Deguelin is administered through i.p. injection daily for 21 days. Animals aremonitored daily for the signs of drug/vehicle associated toxicity and weighed once weekly. Growth of tumor atthe site of cell injection is monitored every alternate day and o

17、f tumor size is measured using calipers. Tumorvolume is calculated by using the well-established formula: tumor volume (mm3)=/6 lengthwidthdepth.Data represent the mean tumor volume+SE (mm3) in each group. The animals are sacrificed at the indicatedtime unless they appear to be moribund or tumors sh

18、ow sign of necrosis. At termination, the tumor isexcised, freed from connective tissue and other organs, a small piece is fixed in 10% buffered formalin andremaining tumor is snap frozen for future biochemical analysis. Liver, lung, kidney and spleen are excisedand weighed.MCE has not independently

19、confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Int J Mol Med. 2018 Jun;41(6):3157-3166.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Mehta R, et al. Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells. PLoS One. 2013 Jun10;8(6):e65113.2. Yang YL, et al. Deguelin induces both apoptosis and auto