奧貝膽酸作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetObeticholic acidCat. No.: HY-12222CAS No.: 459789-99-2分式: CHO分量: 420.63作靶點: FXR; Autophagy作通路: Metabolic Enzyme/Protease; Autophagy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 (237.74 mM)Ethanol : 50 mg/mL (118.87 mM)* means solub

2、le, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 2.3774 mL 11.8869 mL 23.7739 mL5 mM 0.4755 mL 2.3774 mL 4.7548 mL10 mM 0.2377 mL 1.1887 mL 2.3774 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

3、 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: 4.76 mg/mL (11.32 mM); Clear solution此案可獲得 4.76 m

4、g/mL (11.32 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 47.600002 mg/mL 的澄清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: 5 mg/mL (11.89 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 5 mg/mL (11.89 mM，飽和度未知) 的澄清

5、溶液。以 1 mL 作液為例，取 100 L 50.0 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: 5 mg/mL (11.89 mM); Clear solution此案可獲得 5 mg/mL (11.89 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 50.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。4. 請依序添加每種溶劑： 10% EtOH 40%

6、 PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.94 mM); Clear solution此案可獲得 2.5 mg/mL (5.94 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 EtOH 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。5. 請依序添加每種溶劑： 10% EtOH 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (

7、5.94 mM); Clear solution此案可獲得 2.5 mg/mL (5.94 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 EtOH 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。6. 請依序添加每種溶劑： 10% EtOH 90% corn oilSolubility: 2.5 mg/mL (5.94 mM); Clear solution此案可獲得 2.5 mg/mL (5.94 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

8、 mg/mL 的澄 EtOH 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Obeticholic acid (INT-747)種有效的，選擇性的和服活性的 FXR 激動劑，EC50 為 99 nM，并具有抗膽堿和抗炎作。Obeticholic acid 還可誘導(dǎo)細(xì)胞噬 (autophagy)。IC & Target EC50: 99 nM (FXR)體外研究 Obeticholic acid (INT-747) increases the expression of FXR-regulated genes in rat hepatocytes1. Ob

9、eticholic acid(INT-747) reduces expression of liver JNK-1 and JNK-22. Obeticholic acid (INT-747) (256 g/mL) shows completeinhibition of bacterial growth in all strains tested. Intestinal permeability remains unaffected after INT-747-addition toan IFN-exposed intestinal epithelium of Caco-2 cells3.體內(nèi)

10、研究 Obeticholic acid (INT-747) (10 mg/kg/day) completely reverted cholestasis induced by E217. Administration ofObeticholic acid (INT-747) partially prevents the impairment in total bile acid output caused by E217 by increasing the relative abundance of -MCA and TCDCA and TDCA1. Obeticholic acid (INT

11、-747)7 (10 mg/kg) and HS increasesthe pulmonary congestion in the animals. INT-747 does not improve renal pathology in the HS-fed animals2.Obeticholic acid (INT-747) (5 mg/kg) significantly increases survival in BDL rats. Obeticholic acid (INT-747)-treatedBDL rats exhibits a significant selective il

12、eal increase in expression of pore-closing claudin-1. Ileal expression of ZO-1is significantly up-regulated in INT-747-treated BDL rats3.PROTOCOLAnimal Initially, all animals (at 6-weeks age) are placed on a standard rodent diet for a week. Baseline blood and urinePage 2 of 3 www.MedChemEAdministrat

13、ion 2 samples are collected and basal blood pressure (BP) is measured prior to grouping the animals. Subsequently, theanimals are randomized into low (LS; n=9) or high salt (HS) diet groups. Hypertension is induced in the HS group bydaily high-salt diet feeding and the group is subdivided to receive

14、 one of two doses of INT-747: low dose (10mg/kg/day; n=15) or high dose (30 mg/kg/day; n=15) in 1% methylcellulose; or vehicle (1% methylcellulose indistilled water; n=15) orally everyday for 6 weeks. In parallel, the LS group also receive 1% methylcellulose. BP ismeasured weekly for the duration of

15、 the study as described below.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) Cell Host Microbe. 2018 Sep 12;24(3):353-363.e5. J Am Soc Nephrol. 2018 Nov;29(11):2658-2670. Cells. 2019 Nov. J Pharm Anal. 2020 Jan. Int J Mol Sci. 2019 Apr 2;20

16、(7). pii: E1629.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Fiorucci S, et al. Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J Pharmacol Exp Ther.2005 May;313(2):604-12.2. Ghebremariam YT, et

17、al. FXR agonist INT-747 upregulates DDAH expression and enhances sensitivity in high-salt fed Dahl rats. PLoS One. 2013 Apr4;8(4):e60653.3. Verbeke L, et al. The FXR Agonist Obeticholic Acid Prevents Gut Barrier Dysfunction and Bacterial Translocation in Cholestatic Rats. Am J Pathol. 2015Feb;185(2):409-19.4. Pellicciari R, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activ