Obeticholic Acid (Synonyms: INT 747, Obeticholic Acid) |
| Catalog No.GC14158 |
Obeticholic Acid (INT-747; 6-ECDCA; 6-Ethylchenodeoxycholic acid) is a potent, selective and orally active farnesoid X receptor(FXR) agonist with an EC50 of 99nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 459789-99-2
Sample solution is provided at 25 µL, 10mM.
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Obeticholic Acid (INT-747; 6-ECDCA; 6-Ethylchenodeoxycholic acid) is a potent, selective and orally active farnesoid X receptor(FXR) agonist with an EC50 of 99nM[1]. FXR is a ligand-dependent transcription factor belonging to the nuclear hormone receptor superfamily that plays an important role in bile acid, lipid metabolism, carbohydrate homeostasis and inflammatory response[2]. Obeticholic Acid is a semisynthetic hydrophobic bile acid analog used to treat primary biliary cholangitis(PBC) and non-alcoholic steatohepatitis(NASH)[3].
In vitro, treatment of HepG2, Huh7 and SNU-449 cells with Obeticholic Acid (0.01-100µM) for 72h significantly inhibited cell proliferation with IC50 values of 1.067μM, 1.038μM and 0.706μM, respectively, and also inhibited cell migration and invasion[4]. Treatment of primary cultures of human intrahepatic cholangiocarcinoma(iCCA) with Obeticholic Acid (0-2.5µM) for 3-10 days significantly inhibited the proliferation of mucinous and mixed iCCA cells and upregulated FXR gene expression[5].
In vivo, oral treatment of mice with NASH with Obeticholic Acid (10mg/kg) for 4 or 8 weeks significantly inhibited the number of hepatic coronary structures(hCLS), reduced the area of fibrosis and the mRNA expression of fibrotic genes, and long-term treatment had no effect on the body weight and adipose tissue weight of mice[6]. Oral treatment of rats with ascites cirrhosis with Obeticholic Acid (5mg/kg) for 2 weeks significantly reduced intestinal bacterial translocation, reduced intestinal immune cell infiltration, and normalized the expression of inflammatory cytokines[7].
References:
[1] Pellicciari R, Fiorucci S, Camaioni E, et al. 6α-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity[J]. Journal of medicinal chemistry, 2002, 45(17): 3569-3572.
[2] Shaik F B, Prasad D V R, Narala V R. Role of farnesoid X receptor in inflammation and resolution[J]. Inflammation Research, 2015, 64: 9-20.
[3] Chapman R W, Lynch K D. Obeticholic acid—a new therapy in PBC and NASH[J]. British medical bulletin, 2020, 133(1): 95-104.
[4] Attia Y M, Tawfiq R A, Ali A A, et al. The FXR agonist, obeticholic acid, suppresses HCC proliferation & metastasis: role of IL-6/STAT3 signalling pathway[J]. Scientific reports, 2017, 7(1): 12502.
[5] Di Matteo S, Nevi L, Costantini D, et al. The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma[J]. PLoS One, 2019, 14(1): e0210077.
[6] Goto T, Itoh M, Suganami T, et al. Obeticholic acid protects against hepatocyte death and liver fibrosis in a murine model of nonalcoholic steatohepatitis[J]. Scientific reports, 2018, 8(1): 8157.
[7] Úbeda M, Lario M, Muñoz L, et al. Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats[J]. Journal of hepatology, 2016, 64(5): 1049-1057.
| Cell experiment [1]: | |
Cell lines | HepG2, Huh7, and SNU-449 cells |
Preparation Method | 1.2 to 1.8×103 cells per well were seeded in 96-well plates and cultured overnight. Then, the cells were treated with 0.01-100μM of Obeticholic Acid, or DMSO. After 72h, MTT reagent was added to the cells in each well followed by incubation for 2h, and the absorbance was determined using a microplate reader. The effect of treatments on cell viability was presented as the percentage of the absorbance at 570nm from treated cells versus that from untreated control cells. |
Reaction Conditions | 0.01-100µM; 72h |
Applications | Obeticholic Acid reduced the proliferation rates of HepG2, Huh7, and SNU-449 cells with IC50 values of 1.067μM, 1.038μM, and 0.706μM, respectively. |
| Animal experiment [2]: | |
Animal models | MC4R-KO mice |
Preparation Method | 8-week-old MC4R-KO mice were fed Western diet(WD) for 20 weeks, and control WT mice were fed Standard diet(SD) for the same period. MC4R-KO mice fed WD for 6 weeks received a single intraperitoneal injection of CCl4 diluted 1:20 in olive oil at a dose of 0.2ml/kg. After the onset of non-alcoholic steatohepatitis(NASH) symptoms, MC4R-KO mice were gavaged once daily with 10mg/kg Obeticholic Acid or vehicle (0.5% carboxymethyl cellulose) for 4 or 8 weeks. At the end of the experiment, mice were sacrificed under intraperitoneal pentobarbital anesthesia. |
Dosage form | 10mg/kg; p.o. |
Applications | Obeticholic Acid treatment significantly inhibited the number of hepatic crown-like structure(hCLS) and reduced the fibrotic area and mRNA expression of fibrogenic genes. Long-term treatment with Obeticholic Acid had no effect on body weight and adipose tissue weight in MC4R-KO mice. |
References: [1]Attia Y M, Tawfiq R A, Ali A A, et al. The FXR agonist, obeticholic acid, suppresses HCC proliferation & metastasis: role of IL-6/STAT3 signalling pathway[J]. Scientific reports, 2017, 7(1): 12502. [2]Goto T, Itoh M, Suganami T, et al. Obeticholic acid protects against hepatocyte death and liver fibrosis in a murine model of nonalcoholic steatohepatitis[J]. Scientific reports, 2018, 8(1): 8157. | |
| Cas No. | 459789-99-2 | SDF | |
| Synonyms | INT 747, Obeticholic Acid | ||
| 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 | ||
| Canonical SMILES | CCC1C2CC(CCC2(C3CCC4(C(C3C1O)CCC4C(C)CCC(=O)O)C)C)O | ||
| Formula | C26H44O4 | M.Wt | 420.63 |
| Solubility | ≥ 21.5mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 6 reference(s) in Google Scholar.)
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