小白菊内酯作用机制 - Medchemexpress - MCE中国

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

2、soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储

3、存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (8.38 mM); Clear solution此案可获得 2.

4、08 mg/mL (8.38 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (8.38 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.08 mg/mL (8.38 mM，饱和度未知) 的澄

5、清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (8.38 mM); Clear solution此案可获得 2.08 mg/mL (8.38 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活

6、性 Parthenolide在药草短匹菊中发现的倍半萜内酯。 Parthenolide通过抑制 NF-B 活化表现出抗炎活性; 它还可抑制 HDAC1 蛋不影响其他I/II类HDAC。IC & Target NF-B Autophagy Mitophagy体外研究 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.体内研究 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.户使本产品发表的科研献 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