Obeticholic Acid (INT-747) | FXR agonist | CAS 459789-99-2

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Quality Control

Batch: Purity: 99.77%

99.77

Related Targets	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Other FXR Inhibitors	GW4064 Guggulsterone E&Z Turofexorate Isopropyl (XL335) fexaramine BAR502 Nidufexor (LMB-763) Tropifexor (LJN452) Mebhydroline Vonafexor (EYP001) Cilofexor (GS-9674)

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
insect cells	Function assay		1 hr	Agonist activity at recombinant human GST-tagged FXR ligand binding domain (193 to 472 residues) expressed in baculovirus infected insect cells assessed as induction of interaction with biotin labelled SRC-1 after 1 hr by HTRF assay, EC50 = 0.01 μM.	29148806
HEK293T	Function assay		24 hrs	Agonist activity at human FXR expressed in HEK293T cells assessed as BSEP promoter driven cellular transcriptional activity after 24 hrs by luciferase reporter gene assay, EC50 = 0.042 μM.	29148806
COS1	Function assay			Agonist activity at FXR expressed in COS1 cells by cell-based bioluminescence assay, EC50 = 0.099 μM.	20014870
HeLa	Function assay		24 hrs	Agonist activity at human full length FXR expressed in HeLa cells cotransfected with pSG5-human RXR after 24 hrs by Dual-Glo luciferase reporter gene assay, EC50 = 0.16 μM.	25934227
HeLa	Function assay			Agonist activity at human FXR expressed in human HeLa cells assessed as receptor activation by BSEP promoter-driven firefly luciferase reporter gene assay, EC50 = 0.16 μM.	25255039
insect cells	Function assay		1 hr	Agonist activity at recombinant human GST-tagged FXR LBD (193 to 472 residues) expressed in baculovirus-infected insect cells assessed as recruitment of biotinylated SRC1 peptide measured after 1 hr by Alphascreen assay, EC50 = 0.18 μM.	29259742
COS1	Function assay		5 hrs	Agonist activity at human FXR expressed in COS1 cells after 5 hrs by CRE-driven luciferase reporter gene assay, EC50 = 0.361 μM.	17685603
CHO	Function assay		5 hrs	Agonist activity at human TGR5 expressed in CHO cells after 5 hrs by CRE-driven luciferase reporter gene assay, EC50 = 0.755 μM.	17685603
HEK293	Function assay		1 hr	Agonist activity at human TGR5 expressed in HEK293 cells assessed as increase in intracellular cAMP level after 1 hr by TR-FRET assay, EC50 = 0.84 μM.	29259742
NCI-H716	Function assay			Agonist activity at human TGR5 receptor expressed in NCI-H716 cells assessed as intracellular cAMP level by TR-FRET assay, EC50 = 20 μM.	21459580
HepG2	Function assay	20 uM		Induction of FXR-mediated SHP mRNA expression in human HepG2 cells at 20 uM by RT-PCR	21459580
HepG2	Function assay	1 uM		Induction of FXR-mediated SHP mRNA expression in human HepG2 cells at 1 uM by RT-PCR	21459580
HepG2	Function assay	20 uM		Induction of FXR-mediated BSEP mRNA expression in human HepG2 cells at 20 uM by RT-PCR	21459580
HepG2	Function assay	20 uM		Induction of FXR-mediated Ostbeta mRNA expression in human HepG2 cells at 20 uM by RT-PCR	21459580
HepG2	Function assay	1 uM		Induction of FXR-mediated down-regulation of Cyp7A1 mRNA expression in human HepG2 cells at 1 uM by RT-PCR	21459580
HepG2	Function assay	20 uM		Induction of FXR-mediated down-regulation of Cyp7A1 mRNA expression in human HepG2 cells at 20 uM by RT-PCR	21459580
HepG2	Function assay	20 uM		Agonist activity at human FXR expressed in HepG2 cells assessed as renilla luciferase activity at 20 uM by luciferase based transactivation assay	21459580
HepG2	Function assay	1 uM		Induction of FXR-mediated BSEP mRNA expression in human HepG2 cells at 1 uM by RT-PCR	21459580
HepG2	Function assay	1 uM		Induction of FXR-mediated Ostbeta mRNA expression in human HepG2 cells at 1 uM by RT-PCR	21459580
HepG2	Function assay	10 uM		Transactivation of human FXR transfected in human HepG2 cells at 10 uM by beta-galactosidase reporter gene assay	24387325
HepG2	Function assay	10 uM	18 hrs	Agonist activity at FXR in human HepG2 cells assessed as upregulation of OST-alpha mRNA expression at 10 uM after 18 hrs by RT-PCR analysis	24387325
GLUTag	Function assay			Agonist activity at GP-BAR1 in mouse GLUTag cells assessed as increase in intracellular cAMP level	24387325
HepG2	Function assay	10 uM	18 hrs	Agonist activity at FXR in human HepG2 cells assessed as upregulation of SHP mRNA expression at 10 uM after 18 hrs by RT-PCR analysis	24387325
HepG2	Function assay	10 uM	18 hrs	Agonist activity at FXR in human HepG2 cells assessed as upregulation of BESP mRNA expression at 10 uM after 18 hrs by RT-PCR analysis	24387325
GLUTag	Function assay			Agonist activity at GP-BAR1 in mouse GLUTag cells assessed as increase in GLP-1 release	24387325
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 84 mg/mL (199.7 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 84 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.250mg/ml (10.10mM)	Taking the 1 mL working solution as an example, add 50 μL of 85 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.100mg/ml (2.62mM)	Taking the 1 mL working solution as an example, add 50 μL of 22 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	420.63	Formula	C₂₆H₄₄O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	459789-99-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	6-ECDCA, 6-Ethylchenodeoxycholic acid			Smiles	CCC1C2CC(CCC2(C3CCC4(C(C3C1O)CCC4C(C)CCC(=O)O)C)C)O

Mechanism of Action

Targets/IC₅₀/Ki	FXR 99 nM(EC50)
In vitro	In HuH7 cells, Obeticholic Acid (INT-747) acts as a potent FXR agonist with EC50 of 85 nM.
Kinase Assay	Binding Potency of Obeticholic Acid to FXR
Kinase Assay	Obeticholic Acid (INT-747) was tested in an established cell-free ligand sensing assay, which measures the ligand-dependent recruitment of an SRC1 peptide to FXR by fluorescence resonance energy transfer.
In vivo	In rat cholestasis model, Obeticholic Acid (INT-747) promotes bile flow and protects hepatocytes against acute necrosis caused by LCA. This compound (p.o.) improves proteinuria, ameliorates renal structural changes, and modulates renal inflammation and oxidative stress in WD-fed DBA mice. In thioacetamide (TAA)-intoxicated and bile-duct-ligated (BDL) rats, it (30 mg/kg p.o.) reactivates the FXR downstream signaling pathway and decreases portal pressure by lowering total IHVR without deleterious systemic hypotension.
References	[1] https://pubmed.ncbi.nlm.nih.gov/12166927/ [2] https://pubmed.ncbi.nlm.nih.gov/19776172/ [3] https://pubmed.ncbi.nlm.nih.gov/24259407/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-IRE1α XBP1s		29377207

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05740631	Recruiting	Healthy	Universitaire Ziekenhuizen KU Leuven\|Intercept Pharmaceuticals	August 22 2022	Not Applicable
NCT02633956	Completed	Nonalcoholic Steatohepatitis	Intercept Pharmaceuticals	December 4 2015	Phase 2
NCT02548351	Terminated	Non Alcoholic Steatohepatitis (NASH)	Intercept Pharmaceuticals	September 22 2015	Phase 3

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

Question 1:
What formulation can we use to dissolve it for mice in vivo study?

Answer:
You can use the vehicle of: 1% wt/vol methyl-cellulose as indicated in this paper, http://www.sciencedirect.com/science/article/pii/S0925443911000883 "daily oral gavage with 5 mg/kg/day of this compound or vehicle (1% wt/vol methyl-cellulose) from 3 days prior to induction of colitis"

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Obeticholic Acid (INT-747) FXR agonist

Chemical Structure

Molecular Weight: 420.63