楝酰胺作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetRocaglamideCat. No.: HY-19356CAS No.: 84573-16-0分式: CHNO分量: 505.56作靶點: NF-B; HSP; Eukaryotic Initiation Factor (eIF)作通路: NF-B; Cell Cycle/DNA Damage; Metabolic Enzyme/Protease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 (296.70 mM

2、; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.9780 mL 9.8900 mL 19.7800 mL5 mM 0.3956 mL 1.9780 mL 3.9560 mL10 mM 0.1978 mL 0.9890 mL 1.9780 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

3、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 Vitro 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: 7.5 mg/mL (14.84 mM); Clear solution此案可獲得 7.5 mg/mL (14.84

4、mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 75.0 mg/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: 7.5 mg/mL (14.84 mM); Clear solution此案可獲得 7.5 mg/mL (14.84 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例

5、，取 100 L 75.0 mg/mL 的澄均勻。DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合BIOLOGICAL ACTIVITY物活性 Rocaglamide (Roc-A) 從 Aglaia 中分離出來，可于咳嗽，受傷，哮喘和炎癥性膚病。Rocaglamide T 細(xì)胞中 種有效的 NF-B 活化抑制劑。Rocaglamide 種有效的選擇性熱休克因 1 (HSF1) 活化抑制劑，IC50 約為 50 nM。Rocaglamide 還抑制翻譯起始因 eIF4A 的功能。Rocaglamide 還具有抗癌特性。IC & Target HSF150 nM (I

6、C50)體外研究 Rocaglamide enhances TRAIL-induced apoptosis in resistant HCC cells. Treatment with Rocaglamide alone leads toapoptosis in 9% HepG2 and 11% Huh-7 cells and treatment with TRAIL induces apoptosis in 16% HepG2 and 17%Huh-7 cells. However, the combination of Rocaglamide and TRAIL induces apopt

7、osis in 55% HepG2 and 57% Huh-7cells, which is evidently more than an additive effect. A similar result is obtained by measurement of cell viability usingcrystal violet staining. Rocaglamide has the potential to sensitize highly chemoresistant HepG2 and Huh-7 cells toTRAIL-based therapy2.體內(nèi)研究 Tumor

8、volumes in the Rocaglamide-treated group are 4512% compared with the control group. Rocaglamide significantly suppresses tumor growth compared with that in the control group. Treatment with Rocaglamide does not lead to any reduction in body weight and no apparent signs of toxicity are observed in th

9、e mice during thetreatment, suggesting that Rocaglamide is generally tolerated well2.PROTOCOLCell Assay 2 HepG2 and Huh-7 cells (1104/well) are seeded in 96-well plates in complete culture medium and incubated for 24h. The cells are then exposed to 100 nM Rocaglamide and/or 100 ng/mL TRAIL for 24 h.

10、 The control cells are treatedwith DMSO at a concentration equal to that used for the drug-treated cells. The complete culture medium is thenremoved and MTT (200 L, 0.5 mg/mL in 10% FBS-containing DMEM) is added to each well and the plate isincubated for 2 h at 37C in a humidified incubator. The sol

11、ution is then removed from the wells and 200 L DMSO isadded to each well prior to agitation. The absorbance at 570 nm is read using a microplate reader (Bio-Tek ELx800).The value for the vehicle-treated cells is considered to indicate 100% viability. Furthermore, a crystal violet assay iscarried out

12、. Briefly, the cells (1105/mL) are seeded in a 12 well plate for 12 h, and treated with TRAIL (0-100 ng/mL)and/or RocA(1-100 nM) for 12 h. The treated cells are washed with phosphate-buffered saline (PBS), fixed with 4%paraformaldehyde for 15 min, and stained using crystal violet for a further 30 mi

13、n2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice2Administration 2 The Huh-7 cells (3106), suspended in 100 L mix (equal volumes of DMEM and Matrigel), are implantedsubcutaneously into the right flank of 10 female SCID mice (6-week-old) and

14、 then randomly divided into two equalgroups, one of which received an intraperitoneal injection of Rocaglamide (2.5 mg/kg in 80 L olive oil; n=5) and theother, used as a vehicle control, received olive oil alone (n=5). These treatments are performed once daily for 32 daysand the tumor volumes and bo

15、dy weights of the animals are measured twice a week. The tumor volumes (mm3) arecalculated using the following formula: Tumor volume=LS2/2, where L is the longest diameter and S is the shortest.At the end of the experiments, the mice are sacrificed and tumor samples are harvested, fixed in formalin

16、andembedded in paraffin as tissue sections for immunohistochemical analysis.Page 2 of 3 www.MedChemEMCE 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) Autophagy. 2020 Mar;16(3):419-434. Mol Cancer Res. 2019 Nov 19. pii: molcanres.0217.2019. Fro

17、nt Pharmacol. 2019 Sep 3;10:968.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Santagata S, et al. Tight coordination of protein translation and heat shock factor 1 activation supports the anabolic malignant state. Science. 2013 Jul19; 341(6143): 1238303.2. Luan Z,

18、et al. Rocaglamide overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells byattenuating the inhibition of caspase-8 through cellular FLICE-like-inhibitory protein downregulation. Mol Med Rep3. Baumann B, et al. Rocaglamide derivatives are potent inhibitors of NF-kappa B activation in