吡非尼酮作用機制 - Medchemexpress - MCE中國

1、Product Data SheetPirfenidoneCat. No.: HY-B0673CAS No.: 53179-13-8分式: CHNO分量: 185.22作靶點: TGF-beta/Smad; CCR作通路: Stem Cell/Wnt; TGF-beta/Smad; GPCR/G Protein; Immunology/Inflammation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 (539.90 mM)* means sol

2、uble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 5.3990 mL 26.9949 mL 53.9898 mL5 mM 1.0798 mL 5.3990 mL 10.7980 mL10 mM 0.5399 mL 2.6995 mL 5.3990 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

3、，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?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，適當保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 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: 2.5 mg/mL (13.50 mM); Clear solution此案可獲得 2.5

4、mg/mL (13.50 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 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: 2.5 mg/mL (13.50 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (13.50 mM，飽和度未知) 的澄清溶

5、液。以 1 mL 作液為例，取 100 L 25.0 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: 2.5 mg/mL (13.50 mM); Clear solution此案可獲得 2.5 mg/mL (13.50 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 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性

6、Pirfenidone (AMR69)種抗纖維化劑，可減弱纖維細胞中 CCL2 和 CCL12 的產(chǎn)。Pirfenidone 具有抑制細胞長的作，并能降低膠質(zhì)瘤細胞系中的 TGF-2 蛋平。Pirfenidone 還具有抗炎活性。IC & Target TGF-21體外研究 Pirfenidone (PFD) reduces the protein levels of the matrix metalloproteinase (MMP)-11, a TGF- target gene and furinsubstrate involved in carcinogenesis. These dat

7、a define PFD or PFD-related agents as promising agents for humancancers associated with enhanced TGF- activity1. In RAW264.7 cells, a murine macrophage-like cell line, Pirfenidonesuppresses the proinflammatory cytokine TNF- by a translational mechanism, which is independent of activation ofthe MAPK2

8、, p38 MAPK, and JNK. In the murine endotoxin shock model, Pirfenidone potently inhibits the productionof the proinflammatory cytokines, TNF-, interferon-, and interleukin-6, but enhances the production of the anti-inflammatory cytokine, interleukin-102. Pirfenidone (PFD) shows its inhibitory effects

9、 on the proliferation of HLECs.Cell proliferation is attenuated in the 0.3 mg/mL group after 24 hours compare with the control group (P=0.044). Theeffect is more apparent in the 0.5 mg/mL group at 24, 48, and 72 hours (P0.05). The proliferation is almostcompletely inhibited with 1 mg/mL PFD at all t

10、he time-points (P0.01)3.體內(nèi)研究 Administration of Pirfenidone (300 mg/kg/day) for 4 wk. Pirfenidone significantly attenuates the score whenadministered in Bleomycin (BLM)-treated mice (P0.0001). Moreover, collagen content is quantified in the lungs toevaluate the anti-fibrotic effects of Pirfenidone. T

11、he collagen content in the lungs of BLM-treated mice is significantlyincreased compared with that in saline- or Pirfenidone-treated mice, and this increase is significantly attenuated byPirfenidone administration on day 28 after BLM treatment (P=0.0012)4.PROTOCOLCell Assay 3 HLECs are seeded in 96-w

12、ell plates (1104 cells/well) for 24 hours in -MEM/10% FBS/1%NEAA, and are cultured instationary tubes in serum-free medium for 24 hours. And then the culture medium is removed and cells are bathed in-MEM with 10% FBS and 1% NEAA supplemented with 0, 0.01, 0.1, 0.2, 0.3, 0.5, or 1 mg/mL Pirfenidone f

13、or 0, 4, 12,24, 48, or 72 hours. After incubation with 180 L -MEM and 20 L of 5 mg/mL MTT for 4 hours at 37C, the MTTsolution is discarded. The Formosan precipitates are dissolved in 180 L DMSO by agitating the dishes for 10 minutesat 200 rpm on an orbital shaker. The absorbance at 490 nm in each we

14、ll is read with a micro plate reader. We furtherexamined the effects of PFD by refining the concentrations at 0.2, 0.25, 0.3, 0.4, 0.5 and 0.6 mg/mL using the MTTassay3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice4Administration 4 Nine-we

15、ek-old female C57BL/6 mice are used. Pirfenidone is administered orally for 14 days after osmotic pumpimplantation. The volume of administration is determined according to body weight. Animals are allocated into 4Page 2 of 3 www.MedChemEgroups (n=6/group): normal control, BLM, Pirfenidone (300 mg/kg

16、/day), and BLM + Pirfenidone. The Pirfenidonedose is selected according to a report published elsewhere. Pirfenidone is also administered in a therapeutic settingbeginning at day 10 to assess the effect of the drug on the fibrotic phase of BLM model mice.MCE has not independently confirmed the accur

17、acy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Pharm Res. 2020 Feb 24;37(3):59. J Ethnopharmacol. 2019 Apr 12:111878. Radiat Res. 2018 Oct;190(4):396-403. Pathol Res Pract. 2019 Jul 27:152568. Oncotarget. 2018 May 4;9(34):23462-23481.See more customer validations on HYPERLINK www.MedC

18、hemE www.MedChemEREFERENCES1. Burghardt I, et al. Pirfenidone inhibits TGF-beta expression in malignant glioma cells. Biochem Biophys Res Commun. 2007 Mar 9;354(2):542-7.2. Nakazato H, et al. A novel anti-fibrotic agent pirfenidone suppresses tumor necrosis factor-alpha at the translational level. Eur J Pharmacol. 2002 Jun20;446(1-3):177-85.3. Yang Y, et al. Inhibition of Pirfenidone on TGF-beta2 induced proliferation, migration and epithlial-mesenchymal transitionof human lens epithelial ce