1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEObeticholic acidCat. No.: HY-12222CAS No.: 459789-99-2Synonyms: INT-747; 6-ECDCA; 6-Ethylchenodeoxycholic acid分式: CHO分量: 420.63作靶點: FXR作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C

2、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 soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration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，并請注意儲

3、備液的保存式和期限。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?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：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 solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)1/3 Maste

4、r of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 5 mg/mL (11.89 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 5 mg/mL (11.89 mM); Clear solution4. 請依序添加每種溶劑： 10% EtOH 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.94 mM); Clear solution5. 請依序添加每種溶劑： 10% EtOH 90% (20

5、% SBE-CD in saline)Solubility: 2.5 mg/mL (5.94 mM); Clear solution6. 請依序添加每種溶劑： 10% EtOH 90% corn oilSolubility: 2.5 mg/mL (5.94 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Obeticholic acid (INT-747)是有效選擇性的法尼醇 X 受體 (FXR) 激動劑， EC50 值為 99 nM。IC50 & Target EC50: 99 nM (FXR)體外研究 Obeticholic acid (INT-747)

6、 increases the expression of FXR-regulated genes in rat hepatocytes 1.Obeticholic acid (INT-747) reduces expression of liver JNK-1 and JNK-2 2. Obeticholic acid (INT-747) (256g/mL) shows complete inhibition of bacterial growth in all strains tested. Intestinal permeability remainsunaffected after IN

7、T-747-addition to an IFN-exposed intestinal epithelium of Caco-2 cells 3.體內(nèi)研究 Obeticholic acid (INT-747) (10 mg/kg/day) completely reverted cholestasis induced by E217. Administrationof Obeticholic acid (INT-747) partially prevents the impairment in total bile acid output caused by E217 byincreasing

8、 the relative abundance of -MCA and TCDCA and TDCA 1. Obeticholic acid (INT-747)7 (10mg/kg) and HS increases the pulmonary congestion in the animals. INT-747 does not improve renalpathology in the HS-fed animals 2. Obeticholic acid (INT-747) (5 mg/kg) significantly increases survival inBDL rats. Obe

9、ticholic acid (INT-747)-treated BDL rats exhibits a significant selective ileal increase inexpression of pore-closing claudin-1. Ileal expression of ZO-1 is significantly up-regulated in INT-747-treatedBDL rats 3.PROTOCOLAnimal Initially, all animals (at 6-weeks age) are placed on a standard rodent

10、diet for a week. Baseline blood andAdministration 2 urine samples are collected and basal blood pressure (BP) is measured prior to grouping the animals.Subsequently, the animals are randomized into low (LS; n=9) or high salt (HS) diet groups. Hypertension isinduced in the HS group by daily high-salt

11、 diet feeding and the group is subdivided to receive one of twodoses of INT-747: low dose (10 mg/kg/day; n=15) or high dose (30 mg/kg/day; n=15) in 1% methylcellulose;or vehicle (1% methylcellulose in distilled water; n=15) orally everyday for 6 weeks. In parallel, the LS groupalso receive 1% methyl

12、cellulose. BP is measured weekly for the duration of the study as described below.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻 Cell Host Microbe. 2018 Sep 12;24(3):353-363.e5. J Am Soc Neph

13、rol. 2018 Nov;29(11):2658-2670. Int J Mol Sci. 2019 Apr 2;20(7). pii: E1629. J Pharmacol Exp Ther. 2019 Aug 12. pii: jpet.119.261099. Life Sci. 2019 Jul 9:116643.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Fiorucci S, et al. Protective effects of 6-ethyl chenodeoxycholic ac

14、id, a farnesoid X receptor ligand, in estrogen-induced cholestasis. JPharmacol Exp Ther. 2005 May;313(2):604-12.2. Ghebremariam YT, et al. FXR agonist INT-747 upregulates DDAH expression and enhances sensitivity in high-salt fed Dahl rats. PLoSOne. 2013 Apr 4;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. 2015 Feb