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.
理化性质和储存条件
| Molecular Weight (MW) | 420.63 |
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| Formula | C26H44O4 |
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| CAS No. | 459789-99-2 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 84 mg/mL (199.7 mM) |
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| Water: <1 mg/mL |
| Ethanol: 84 mg/mL (199.7 mM) |
| SMILES Code | 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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| Synonyms | INT-747, 6-ECDCA; 6-Ethylchenodeoxycholic acid; Obeticholic acid; INT 747; INT747; Ocaliva. |
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实验参考方法
| In Vitro | In vitro activity: Obeticholic Acid (also known as INT747; 6-ECDCA), a novel derivative of cholic acid, is a potent and selective agonist of farnesoid X receptor (FXR) with EC50 of 99 nM. It is a semi-synthetic analog of bile acid which has the chemical structure 6α-ethyl-chenodeoxycholic acid. Obeticholic Acid is used as a drug to treat primary biliary cholangitis, and is undergoing development for several other liver diseases and related disorders.
Kinase Assay: INT-747 is a potent and selective farnesoid X receptor (FXR) agonist with an EC50 of 99 nM.
Cell Assay: 6-ECDCA increases the expression of FXR-regulated genes in rat hepatocytes. INT-747 reduces expression of liver JNK-1 and JNK-2. 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. |
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| In Vivo | Administration of LCA and its conjugates to rodents causes intrahepatic cholestasis,a pathogenic state characterized by decreased bile flow and the accumulation of bile constituents in the liver and blood. In DMH (dimethyldydrazine)-induced murine carcinogenesis model, LCA suppresses apoptosis almost completely in premalignant colon. LCA. |
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| Animal model | Rat cholestasis model |
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| Formulation & Dosage | Dissolved in saline; 7 μmol/kg/min; Infused at the right jugular vein using PE-50 polyethylene tubing |
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| References | J Med Chem. 2002 Aug 15;45(17):3569-72; Am J Physiol Renal Physiol. 2009 Dec;297(6):F1587-96. |
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