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Purity: ≥98%
Obeticholic Acid (INT747; 6-ECDCA; 6-Ethylchenodeoxycholic acid; trade name Ocaliva), a novel derivative of cholic acid, is a potent, orally bioactive and selective agonist of farnesoid X receptor (FXR) with EC50 of 99 nM, and has anticholeretic and anti-inflammatory activities. It is a semi-synthetic analog of bile acid which has the chemical structure 6α-ethyl-chenodeoxycholic acid. Obeticholic Acid was approved in 2016 for use as a drug to treat primary biliary cholangitis, and is undergoing development for several other liver diseases and related disorders. It displays anticholeretic activity in a rat model of cholestasis. It inhibits vascular smooth muscle cell inflammation and migration as well as promotes adipocyte differentiation and regulates adipose cell function in vivo.
| Targets |
FXR (EC50: 99 nM)
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| ln Vitro |
In rat hepatocytes, obeticholic acid (INT-747) elevates the expression of FXR-regulated genes[1]. Liver JNK-1 and JNK-2 expression is decreased by obeticholic acid (INT-747)[2]. In every examined strain, obeticholic acid (INT-747) at 256 μg/mL completely inhibits bacterial growth. After INT-747 is added to an intestinal epithelium of Caco-2 cells that has been exposed to IFN-γ, intestinal permeability is not changed[3].
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| ln Vivo |
The cholestasis caused by E217α was totally reversed by obeticholic acid (INT-747) (10 mg/kg/day). By boosting the relative abundance of β -MCA, TCDCA, and TDCA, the administration of obeticholic acid (INT-747) partially reverses the impairment in total bile acid secretion caused by E217α[1]. In the mice, obeticholic acid (INT-747)7 (10 mg/kg) and HS exacerbate lung congestion. In animals administered HS, INT-747 does not improve renal pathology[2]. In BDL rats, obeticholic acid (INT-747) (5 mg/kg) considerably improves survival. BDL rats treated with obeticholic acid (INT-747) show a substantial increase in the expression of pore-closing claudin-1 only in the ileum. ZO-1 is markedly up-regulated in the ileum in BDL rats treated with INT-747[3].
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| Cell Assay |
The exposure of rat hepatocytes to 1 microM 6-ECDCA caused a 3- to 5-fold induction of small heterodimer partner (Shp) and bile salt export pump (bsep) mRNA and 70 to 80% reduction of cholesterol 7alpha-hydroxylase (cyp7a1), oxysterol 12beta-hydroxylase (cyp8b1), and Na(+)/taurocholate cotransporting peptide (ntcp) [2].
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| Animal Protocol |
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| References |
[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 |
| Molecular Formula |
C26H44O4
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| Molecular Weight |
420.63
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| Exact Mass |
420.323959
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| Elemental Analysis |
C, 74.24; H, 10.54; O, 15.21
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| CAS # |
459789-99-2
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| Related CAS # |
Obeticholic acid-d5;1992000-80-2;Obeticholic Acid-d4
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| Appearance |
White to off-white solid powder
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| LogP |
5.7
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| tPSA |
77.8A^2
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| SMILES |
C[C@@H]([ C@H]1CC[C@@]2([H])[C@]3([H])[ C@H](O)[ C@H](CC)[C@]4([H])C[ C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)CCC(O)=O
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| InChi Key |
ZXERDUOLZKYMJM-ZWECCWDJSA-N
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| InChi Code |
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
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| Chemical Name |
(4R)-4-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3774 mL | 11.8869 mL | 23.7739 mL | |
| 5 mM | 0.4755 mL | 2.3774 mL | 4.7548 mL | |
| 10 mM | 0.2377 mL | 1.1887 mL | 2.3774 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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