| CAS |
No.459789-99-2 |
| 中文名称 |
奥贝胆酸 |
| 英文名称 |
Obeticholic Acid |
| 别名 |
INT-747;6-ECDCA;6-Ethylchenodeoxycholic acid |
| 分子式 |
C26H44O4 |
| 分子量 |
420.63 |
| 溶解性 |
Soluble in DMSO ≥10mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| EC |
EINECS 810-245-2 |
| MDL |
MFCD16621104 |
| SMILES |
CCC1C2CC(CCC2(C3CCC4(C(C3C1O)CCC4C(C)CCC(=O)O)C)C)O |
| InChIKey |
ZXERDUOLZKYMJM-ZWECCWDJSA-N |
| InChI |
InChI=1S/C26H44O4/c1-5-17-21-14-16(27)10-12-26(21，4)20-11-13-25(3)18(15(2)6-9-22(28)29)7-8-19(25)23(20)24(17)30/h15-21，23-24，27，30H，5-14H2，1-4H3，(H，28，29)/t15-，16-，17-，18-，19+，20+，21+，23+，24-，25-，26-/m1/s1 |
| PubChem CID |
447715 |
| 靶点 |
FXR |
| 通路 |
Metabolic Enzyme&Protease |
| 背景说明 |
Obeticholic acid 是一种有效的，选择性的和具有口服活性的 FXR 激动剂。Obeticholic acid 还可诱导细胞自噬 (autophagy)。 |
| 生物活性 |
Obeticholic acid (INT-747) is a potent， selective and orally active FXR agonist with an EC50 of 99 nM. Obeticholic acid has anticholeretic and anti-inflammation effect. Obeticholic acid also induces autophagy.[1-4] |
| In Vitro |
Obeticholic acid (INT-747) 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) (256 μg/mL) shows complete inhibition of bacterial growth in all strains tested. Intestinal permeability remains unaffected after INT-747-addition to an IFN-γ-exposed intestinal epithelium of Caco-2 cells[3]. |
| In Vivo |
Obeticholic acid (INT-747) (10 mg/kg/day) completely reverted cholestasis induced by E217α. Administration of Obeticholic acid (INT-747) partially prevents the impairment in total bile acid output caused by E217α by increasing the relative abundance of β-MCA and TCDCA and TDCA[1]. Obeticholic acid (INT-747)7 (10 mg/kg) and HS increases the pulmonary congestion in the animals. INT-747 does not improve renal pathology in the HS-fed animals[2]. Obeticholic acid (INT-747) (5 mg/kg) significantly increases survival in BDL rats. Obeticholic acid (INT-747)-treated BDL rats exhibits a significant selective ileal increase in expression of pore-closing claudin-1. Ileal expression of ZO-1 is significantly up-regulated in INT-747-treated BDL rats[3]. |
| 动物实验 |
Initially， all animals (at 6-weeks age) are placed on a standard rodent diet for a week. Baseline blood and 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 is induced in the HS group by daily high-salt diet feeding and the group is subdivided to receive one of two doses 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 group also receive 1% methylcellulose. BP is measured weekly for the duration of the study as described below. |
| 数据来源文献 |
[1]. Pellicciari R， et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA)， a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem. 2002 Aug 15;45(17):3569-72.
[2]. 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.
[3]. Ghebremariam YT， et al. FXR agonist INT-747 upregulates DDAH expression and enhances sensitivity in high-salt fed Dahl rats. PLoS One. 2013 Apr 4;8(4):e60653.
[4]. Verbeke L， et al. The FXR Agonist Obeticholic Acid Prevents Gut Barrier Dysfunction and Bacterial Translocation in Cholestatic Rats. Am J Pathol. 2015 Feb;185(2):409-19. |
| 规格 |
5mg |
| 单位 |
瓶 |
中文
英语
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