小白菊內(nèi)酯作用機制 - Medchemexpress - MCE中國

1、Product Data SheetParthenolideCat. No.: HY-N0141CAS No.: 20554-84-1分式: CHO分量: 248.32作靶點: NF-B; Autophagy; Mitophagy; Apoptosis作通路: NF-B; Autophagy; Apoptosis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 : 100 mg/mL (402.71 mM)H2O : 0.1 mg/mL (insoluble)* means

2、soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 4.0271 mL 20.1353 mL 40.2706 mL5 mM 0.8054 mL 4.0271 mL 8.0541 mL10 mM 0.4027 mL 2.0135 mL 4.0271 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

3、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 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: 2.08 mg/mL (8.38 mM); Clear solution此案可獲得 2.

4、08 mg/mL (8.38 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 20.8 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: 2.08 mg/mL (8.38 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.08 mg/mL (8.38 mM，飽和度未知) 的澄

5、清溶液。以 1 mL 作液為例，取 100 L 20.8 mg/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: 2.08 mg/mL (8.38 mM); Clear solution此案可獲得 2.08 mg/mL (8.38 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 20.8 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活

6、性 Parthenolide在藥草短匹菊中發(fā)現(xiàn)的倍半萜內(nèi)酯。 Parthenolide通過抑制 NF-B 活化表現(xiàn)出抗炎活性; 它還可抑制 HDAC1 蛋不影響其他I/II類HDAC。IC & Target NF-B Autophagy Mitophagy體外研究 Parthenolide (PTL) has a dose-dependent growth inhibition effect on NSCLC cells Calu-1, H1792, A549, H1299, H157,and H460. Parthenolide can induce cleavage of apoptoti

7、c proteins such as CASP8, CASP9, CASP3 and PARP1 both inconcentration- and time-dependent manner in tested lung cancer cells, indicating that apoptosis is trigged afterParthenolide exposure. In addition to induction of apoptosis, Parthenolide also induces G0/G1 cell cycle arrest in aconcentration-de

8、pendent manner in A549 cells and G2/M cell cycle arrest in H1792 cells2.體內(nèi)研究 Only Parthenolide, the HDAC inhibitor with anti-inflammatory features, displayed a potent anti-apoptotic effect inPhb1 KO hepatocytes. Indeed, TSA and Parthenolide-treated hepatocytes showed increased levels of FXR, and red

9、uced levels of CYP7A1, HDAC4, TNF, TRAIL and Bax suggesting a less toxic effect of bile acids as a results ofspecific HDAC inhibition, resulting in the attenuation of the Phb1 KO hepatocytes apoptotic response. Importantly,Parthenolide exerts a protective effect from the liver injury after BDL in Ph

10、b1 KO mice. Indeed, Parthenolide treatmentresults in a reduction of the mortality rate of this mice after BDL associated with a lower apoptotic response asrevealed by a reduction of necrotic areas, Tunel-staining, as well as decreased ALT (8431957 vs.4225210 U/L) andAST (4805300 vs.2242438 U/L) acti

11、vities compared to control Phb1 KO mice3.PROTOCOLCell Assay 2 Human lung cancer cell lines are seeded in 96-well plates and treated on the second day with the givenconcentration of Parthenolide (0, 5, 10, 20 M) for another 48 hours and then subjected to SRB or MTT assay. ForSRB assay, live cell numb

12、er is estimated as described earlier. After treatment, the medium is discarded firstly. In orderto fix the adherent cells, 100 L of cold trichloroacetic acid (10% (w/v) are adding to each well and incubating at 4Cfor at least 1 hour. The plates are then washed five times with deionized water and dri

13、ed in the air. Each well are thenadded with 50 L of SRB solution (0.4% w/v in 1% acetic acid) and incubated for 5 min at room temperature. Theplates are washed five times with 1% acetic acid to remove unbound SRB and then air dried. The residual bound SRBis solubilized with 100 L of 10 mM Tris base

14、buffer (pH 10.5), and then read using a microtiter plate reader at 495nm. The MTT assay is executed. 20 L MTT (5 mg/mL) are added to each sample and incubate at 37C for 4 h, then100 L solubilization solution are added. Cell viability is determined at 595 nm2.MCE has not independently confirmed the a

15、ccuracy of these methods. They are for reference only.Animal Mice3Administration 3 Phb1 KO mice are used. Males from 8-12 weeks of age are treated. Parthenolide is intraperitoneally injected at adose of 3 mg/kg 24 h and 1h before bile duct ligation (BDL) or twice a week during two weeks. Liver speci

16、mens arePage 2 of 3 www.MedChemEsnap-frozen for subsequent analysis3.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) Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):2961-2966. Cancer Lett. 2018 Aug 1;428:77-89. J Mol Med (Berl). 2019 Aug;97(8):

17、1183-1193. Biomedical & Life Sciences. 2020 Jan.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Nakshatri H, et al. NF-B-dependent and -independent epigenetic modulation using the novel anti-cancer agent DMAPT. Cell Death Dis. 2015 Jan22;6:e1608.2. Zhao X, et al. Parthenolide induces apoptosis via TNFRSF10B and PMAIP1 pathways in human lung cancer cells. J Exp Clin Cancer Res. 2014 Jan 6;33:3.3. Barbier-Torres L, et al. Histone deacetylase 4 promotes cholestatic liver injury in the absence of pr