Obeticholic Acid

• CAT Number: I003604
• CAS Number: 459789-99-2
• Molecular Formula: C26H44O4
• Molecular Weight: 420.63
• Purity: ≥95%
• Target: FXR
• Solubility: DMSO: ≥ 35 mg/mL
• Storage: Store at -20°C
• IC50: 99 nM(EC50)
• IUPAC 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
• 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
• InChIKey: ZXERDUOLZKYMJM-ZWECCWDJSA-N
• 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

INT-747(Obeticholic acid; 6-ECDCA; CAS 459789-99-2) is a potent and selective FXR agonist(EC50=99 nM) endowed with anticholestatic activity.
IC50 value: 99 nM(EC50) 
Target: FXR agonist
in vitro: 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).
in vivo: In vivo administration of 6-ECDCA protects against cholestasis induced by E(2)17alpha. high salt (HS) diet significantly increased systemic blood pressure. In addition, HS diet downregulated tissue DDAH expression while INT-747 protected the loss in DDAH expression and enhanced insulin sensitivity compared to vehicle controls. Rats were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and then were assessed for changes in gut permeability, BTL, and tight-junction protein expression, immune cell recruitment, and cytokine expression in ileum, mesenteric lymph nodes, and spleen. After INT-747 treatment, natural killer cells and interferon-γ expression markedly decreased, in association with normalized permeability selectively in ileum (up-regulated claudin-1 and occludin) and a significant reduction in BTL.

Overview of Clinical Research

INT-747 is a Farnesoid X-activated receptor agonist. It has been granted for the orphan drug status in Primary biliary cirrhosis; Primary sclerosing cholangitis.

Reference

1:FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats. Ghebremariam YT, Yamada K, Lee JC, Johnson CL, Atzler D, Anderssohn M, Agrawal R, Higgins JP, Patterson AJ, Böger RH, Cooke JP.PLoS One. 2013 Apr 4;8(4):e60653. doi: 10.1371/journal.pone.0060653. Print 2013. PMID: 23593273 Free PMC Article
2:Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome. Morelli A, Comeglio P, Filippi S, Sarchielli E, Cellai I, Vignozzi L, Yehiely-Cohen R, Maneschi E, Gacci M, Carini M, Adorini L, Vannelli GB, Maggi M.J Steroid Biochem Mol Biol. 2012 Oct;132(1-2):80-92. doi: 10.1016/j.jsbmb.2012.02.007. Epub 2012 Mar 8. PMID: 22406511