非諾貝特酸作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetFenofibric acidCat. No.: HY-B0760CAS No.: 42017-89-0分式: CHClO分量: 318.75作靶點(diǎn): PPAR; COX作通路: Cell Cycle/DNA Damage; Immunology/Inflammation儲(chǔ)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(shí)驗(yàn) DMSO : 100 mg/mL (313.73 mM)H2O : 0.1 mg/mL (insoluble)* means sol

2、uble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 3.1373 mL 15.6863 mL 31.3725 mL5 mM 0.6275 mL 3.1373 mL 6.2745 mL10 mM 0.3137 mL 1.5686 mL 3.1373 mL請(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，

3、請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.84 mM); Clear solution此案可獲得 2.5 mg

4、/mL (7.84 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(chǔ)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(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.84 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (7.84 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)

5、驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Fenofibric acid是fenofibrate 的活性代謝物，為 PPAR 激動(dòng)劑，對(duì) PPAR，PPAR 和 PPAR 的 EC50 值分別為 22.4 M，1.47 M 和 1.06 M；Fenofibric acid 同時(shí)可抑制 COX-2 的活性，IC50 值為 48 nM。IC & Target PPAR PPAR PPAR COX-21.06 M (EC50) 1.47 M (EC50) 22.4 M (EC

6、50) 48 M (IC50)體外研究 Fenofibric acid is a PPAR activitor, with EC50s of 22.4 M, 1.47 M, and 1.06 M for PPAR, PPAR and PPAR,respectively1. Fenofibric acid (10, 25, 50, 75, and 100 nM) dose-dependently inhibits COX-2 enzyme, with IC50 of 48nM2. Fenofibric acid (500 nM) reduces abundance of AOX1 protein

7、 in HepG2 cells3. Fenofibric acid (100 M)decreases JNK1/2, c-Jun, and p38 MAPK phosphorylation, and prevents the accumulation of reactive oxygen species,endoplasmic reticulum (ER) stress and disruption of blood retinal barrier (BRB) in response to the combination ofhigh-glucose (HG) and hypoxia in A

8、RPE-19 cells. Fenofibric acid (100 M) activates IGF-IR/Akt/ERK1/2-mediatedsurvival signaling pathways in ARPE-19 cells under HG conditions and hypoxia4.體內(nèi)研究 Fenofibric acid (1, 5, 10 mg/kg, p.o.) shows anti-inflammatory activity in Wistar rats with acute inflammation inducedby carrageenan2.PROTOCOLC

9、ell Assay 4 ARPE-19 cells are cultured under normoglycemic (5.5 mM D-glucose) or hyperglycemic (25 mM D-glucose)conditions for 18 days at 37C under 5% (v/v) CO2 in medium DMEM/F12 supplemented with 10% (v/v) fetal serum(FS) and penicillin/streptomycin. ARPE-19 cells are used and the media is changed

10、 every 3-4 days. The conditionstested are: (1) Control cells which are maintained in 5.5 mM D-glucose (normal glucose) for 18 days. (2) Cells culturedin 5.5 mM D-glucose treated with 100 M Fenofibric acid for 72 h (days 16, 17, and 18; 1 application/day). (3) Cellscultured as in (1) or (2) and submi

11、tted to hypoxia (1% oxygen) for the last 6 or 24 h. (4) Cells maintained in 25 mM D-glucose (HG) for 18 days. (5) Cells cultured in 25 mM D-glucose treated with 100 M Fenofibric acid for 72 h (days16, 17, and 18; 1 application/day). (6)Cells cultured as in (4) or (5) and submitted to hypoxia (1% oxy

12、gen) for the last 6or 24 h4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal The anti-inflammatory activity of fenofibrate and its active metabolite fenofibric acid is assessed by injecting 0.1 mLAdministration 2 of 1% carrageenan solution prepare

13、d in saline (sub-plantar) to the right hind paw of the rats. Rats are divided into 6groups of six animals each. The first group serves as negative control and receives 1% tween-80 in distilled water, 10mL/kg body mass. Group 2 and 3 receive a single dose of fenofibrate and standard drug diclofenac a

14、t 10 mg/kgbody mass, whereas groups 4, 5, and 6 receive 3 doses of Fenofibric acid at 1, 5, and 10 mg/kg body mass,respectively. All the drugs are given orally using gavages 60 min before the injection of 0.1 mL of 1% carrageenanthrough sub-plantar route. The volume of oedema of test and control gro

15、ups is measured using plethysmometer at0, 1, 2, and 3 h after induction of inflammation2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCESPage 2 of 3 www.MedChemE1. Dietz M, et al. Comparative molecular profiling of the PPAR/ activator aleglita

16、zar: PPAR selectivity, activity and interaction with cofactors.ChemMedChem. 2012 Jun;7(6):1101-11.2. Prasad GS, et al. Anti-inflammatory activity of anti-hyperlipidemic drug, fenofibrate, and its phase-I metabolite fenofibric acid: in silico, in vitro, and invivo studies. Inflammopharmacology. 2017

17、Dec 13.3. Neumeier M, et al. Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes invitro. Biochem Biophys Res Commun. 2006 Nov 24;350(3):731-5. Epub 2006 Sep 27.4. Miranda S, et al. Beneficial effects of fenofibrate in retinal pigment epithelium by the modulation of stress and survival signaling under diabeticconditions.