Obeticholic Acid [459789-99-2]
Referencia B4888-100mg
embalaje : 100mg
Marca : APExBIO Technology
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Teléfono : +1 850 650 7790
Obeticholic Acid
Obeticholic Acid (6alpha-ethyl-chenodeoxycholic acid, 6-ECDCA, INT-747) is a potent and selective agonist of FXR with EC50 value of 99 nM [1].
The farnesoid X receptor (FXR) is a nuclear bile acid receptor involved in bile acid homeostasis, liver fibrosis, hepatic and intestinal inflammation and cardiovascular disease [2].
Obeticholic Acid is a potent and selective FXR agonist with anticholeretic activity [1]. Obeticholic Acid is a semisynthetic bile acid derivative and potent FXR ligand. In estrogen-induced cholestasis rats, 6-ECDCA protected against cholestasis induced by 17α-ethynylestradiol (E217α) [2]. In cirrhotic portal hypertension (PHT) rat models, INT-747 (30 mg/kg) reactivated the FXR downstream signaling pathway and reduced portal pressure by lowering total intrahepatic vascular resistance (IHVR) without deleterious systemic hypotension. This effect was associated with an increased eNOS activity [3]. In the Dahl rat model of salt-sensitive hypertension and insulin-resistance (IR), high salt (HS) diet significantly increased systemic blood pressure and downregulated tissue DDAH expression. INT-747 enhanced insulin sensitivity and inhibited the decrease of DDAH expression [4].
References:
[1]. Pellicciari R, Fiorucci S, Camaioni E, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem, 2002, 45(17): 3569-3572.
[2]. Fiorucci S, Clerici C, Antonelli E, et al. Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J Pharmacol Exp Ther, 2005, 313(2): 604-612.
[3]. Verbeke L, Farre R, Trebicka J, et al. Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats. Hepatology, 2014, 59(6): 2286-2298.
[4]. Ghebremariam YT, Yamada K, Lee JC, et al. FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats. PLoS One, 2013, 8(4): e60653.
- 1. Dipankar Bhattacharya, Christine Becker, et al. "Repositioning of a Novel GABA-B Receptor Agonist, AZD3355 (Lesogaberan), for the Treatment of Non-alcoholic Steatohepatitis." Sci Rep. 2021 Oct 21;11(1):20827. PMID:34675338
- 2. Morshead ML, Sedore CA, et al. "Caenorhabditis Intervention Testing Program: the farnesoid X receptor agonist obeticholic acid does not robustly extend lifespan in nematodes." MicroPubl Biol. 2020;2020:10.17912/micropub.biology.000257. PMID:32550518
- 3. Selina Costa. "Characterizing a Novel Ligand for the Farnesoid X Receptor using Transgenic Zebrafish." University of Toronto. Jun-2018.
- 4. Kent, Rebecca. "Effects of Fenofibrate on CYP2D6 and Regulation of ANG1 and RNASE4 by the FXR Agonist Obeticholic Acid." indigo.uic.edu.2017.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 420.63 |
| Cas No. | 459789-99-2 |
| Formula | C26H44O4 |
| Solubility | ≥21.5 mg/mL in DMSO; insoluble in H2O; ≥21.3 mg/mL in EtOH |
| 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-cyclopentapmphenanthren-17-yl]pentanoic acid |
| SDF | Download SDF |
| Canonical SMILES | CCC1C2CC(CCC2(C3CCC4(C(C3C1O)CCC4C(C)CCC(=O)O)C)C)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
| Cell lines | Rat hepatocytes |
| Preparation method | Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
| Reaction Conditions | 24 h |
| Applications | In rat hepatocytes, obeticholic acid transactivates FXR and modulates FXR regulated genes, resulting in increases of Shp and bsep mRNA expression by 3 to 5 fold and reduction of cyp7a1, cyp8b1, and ntcp mRNA expression by 50 to 70% after exposure to FXR ligands. |
| Animal experiment [2]: | |
| Animal models | Male Wistar rats weighing 200-250 g |
| Dosage form | 30 mg/kg |
| Preparation method | Dissolved in 0.75-1.0 mL of freshly prepared methylcellulose (1%) |
| Applications | Obeticholic acid can reactivate downstream FXR signaling pathway and reduces PP in the TAA and BDL (thioacetamide (TAA)-intoxicated and bile-duct–ligated) models without systemic hemodynamic impact. It also restores endothelial function and reduces the total IHVR in experimental cirrhosis |
| Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
| References: 1. Fiorucci S, Clerici C, Antonelli E 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. Epub 2005 Jan 11. 2. Verbeke L, Farre R, Trebicka J et al. Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats. Hepatology. 2014 Jun;59(6):2286-98. | |
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