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Obeticholic acid

Names

[ CAS No. ]:
459789-99-2

[ Name ]:
Obeticholic acid

[Synonym ]:
6α-ethyl-chenodeoxycholic acid
Cholan-24-oic acid, 6-ethyl-3,7-dihydroxy-, (3α,5β,6α,7α,8ξ)-
6alpha-Ethyl-chenodeoxycholic acid
Obeticholic acid
1osv
6-Ethylchenodeoxycholic acid
INT-747
(3α,5β,6α,7α,8ξ)-6-Ethyl-3,7-dihydroxycholan-24-oic acid
UNII-0462Z4S4OZ
6-ECDCA
OCA
CHC

Biological Activity

[Description]:

INT-747 is a potent and selective farnesoid X receptor (FXR) agonist with an EC50 of 99 nM.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> FXR
Research Areas >> Others

[Target]

EC50: 99 nM (FXR)


[In Vitro]

6-ECDCA increases the expression of FXR-regulated genes in rat hepatocytes[1]. INT-747 reduces expression of liver JNK-1 and JNK-2[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[3].

[In Vivo]

6-ECDCA (10 mg/kg/day) completely reverted cholestasis induced by E217α. Administration of 6-ECDCA partially prevents the impairment in total bile acid output caused by E217α by increasing the relative abundance of β-MCA and TCDCA and TDCA[1]. INT-747 (10 mg/kg) and HS increases the pulmonary congestion in the animals.INT-747 does not improve renal pathology in the HS-fed animals[2]. INT-747 (5 mg/kg) significantly increases survival in BDL rats. INT-747-treated BDL rats exhibits a significant selective ileal increase in expression of pore-closing claudin-1. Ileal expression of ZO-1 is significantly up-regulated in INT-747-treated BDL rats[3].

[Animal admin]

Initially, all animals (at 6-weeks age) are placed on a standard rodent diet for a week. Baseline blood and urine samples are collected and basal blood pressure (BP) is measured prior to grouping the animals. Subsequently, the animals are randomized into low (LS; n=9) or high salt (HS) diet groups. Hypertension is induced in the HS group by daily high-salt diet feeding and the group is subdivided to receive one of two doses of INT-747: low dose (10 mg/kg/day; n=15) or high dose (30 mg/kg/day; n=15) in 1% methylcellulose; or vehicle (1% methylcellulose in distilled water; n=15) orally everyday for 6 weeks. In parallel, the LS group also receive 1% methylcellulose. BP is measured weekly for the duration of the study as described below.

[References]

[1]. 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.

[2]. Ghebremariam YT, et al. FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats. PLoS One. 2013 Apr 4;8(4):e60653.

[3]. 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.


[Related Small Molecules]

GW4064 | T0901317 | Tropifexor | INT-767 | Fexaramine | Chenodeoxycholic acid | XL335 | Androsterone | PX20606 trans racemate | BAR502 | Cilofexor | LY2562175

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
562.9±25.0 °C at 760 mmHg

[ Molecular Formula ]:
C26H44O4

[ Molecular Weight ]:
420.625

[ Flash Point ]:
308.3±19.7 °C

[ Exact Mass ]:
420.323975

[ PSA ]:
77.76000

[ LogP ]:
5.68

[ Vapour Pressure ]:
0.0±3.5 mmHg at 25°C

[ Index of Refraction ]:
1.530

Safety Information

[ Hazard Codes ]:
Xi

Related Compounds