Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C26H44O4 |
Molecular Weight | 420.6252 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 11 / 11 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]1(CC[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)[C@H](C)CCC(O)=O
InChI
InChIKey=ZXERDUOLZKYMJM-ZWECCWDJSA-N
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
Molecular Formula | C26H44O4 |
Molecular Weight | 420.6252 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 10 / 11 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Obeticholic acid (also known as INT-747), is a potent, orally bioavailable farnesoid X receptor (FXR) agonist. The key role of the farnesoid X receptor (FXR) as a regulator of bile and cholesterol metabolism in the liver, with preclinical data from numerous studies providing strong rationale for the advancement of FXR agonists as hepatoprotective therapeutics in chronic liver disease. Obeticholic acid is marketed under the trade name Ocaliva. Ocaliva is specifically indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
0.09 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | OCALIVA Approved UseOCALIVA, a farnesoid X receptor (FXR) agonist, is indicated for the treatment
of primary biliary cholangitis (PBC) in combination with ursodeoxycholic
acid (UDCA) in adults with an inadequate response to UDCA, or as
monotherapy in adults unable to tolerate UDCA. Launch Date1.46430715E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
68.3 ng/mL |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
OBETICHOLIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
747 ng × h/mL |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
OBETICHOLIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
OBETICHOLIC ACID plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
10 mg 1 times / day multiple, oral Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: |
unhealthy, 56 years (range: 29 - 86 years) n = 73 Health Status: unhealthy Condition: primary biliary cholangitis Age Group: 56 years (range: 29 - 86 years) Sex: M+F Population Size: 73 Sources: |
Disc. AE: Pruritus... AEs leading to discontinuation/dose reduction: Pruritus (10%) Sources: |
50 mg 1 times / day multiple, oral Overdose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: |
Other AEs: Ascites, Jaundice... Other AEs: Ascites Sources: Jaundice Portal hypertension Primary biliary cholangitis |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Pruritus | 10% Disc. AE |
10 mg 1 times / day multiple, oral Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: |
unhealthy, 56 years (range: 29 - 86 years) n = 73 Health Status: unhealthy Condition: primary biliary cholangitis Age Group: 56 years (range: 29 - 86 years) Sex: M+F Population Size: 73 Sources: |
Ascites | 50 mg 1 times / day multiple, oral Overdose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: |
|
Jaundice | 50 mg 1 times / day multiple, oral Overdose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: |
|
Portal hypertension | 50 mg 1 times / day multiple, oral Overdose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: |
|
Primary biliary cholangitis | 50 mg 1 times / day multiple, oral Overdose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000PharmR.pdf#page=32 Page: 32.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Identification of a nuclear receptor for bile acids. | 1999 May 21 |
|
Nuclear receptors and lipid physiology: opening the X-files. | 2001 Nov 30 |
|
6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. | 2002 Aug 15 |
|
The methyl transferase PRMT1 functions as co-activator of farnesoid X receptor (FXR)/9-cis retinoid X receptor and regulates transcription of FXR responsive genes. | 2005 Aug |
|
A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis. | 2005 Aug |
|
Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. | 2005 May |
|
Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor gamma contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis. | 2005 Oct |
|
The farnesoid X receptor FXRalpha/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution. | 2007 Sep |
|
Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. | 2011 Apr |
|
FXR protects lung from lipopolysaccharide-induced acute injury. | 2012 Jan |
Patents
Sample Use Guides
Starting Dosage: The recommended starting dosage of OCALIVA is 5
mg orally once daily in adults who have not achieved an adequate
response to an appropriate dosage of UDCA for at least 1 year or are
intolerant to UDCA.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12166927
In HuH7 cells, Obeticholic Acid acts as a potent FXR agonist with EC50 of 85 nM.
Substance Class |
Chemical
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Record UNII |
0462Z4S4OZ
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Record Status |
Validated (UNII)
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NDF-RT |
N0000192561
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NCI_THESAURUS |
C1636
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EU-Orphan Drug |
EU/3/10/753
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FDA ORPHAN DRUG |
253207
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FDA ORPHAN DRUG |
259008
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WHO-ATC |
A05AA04
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FDA ORPHAN DRUG |
937523
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43602
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M11955
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DB05990
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0462Z4S4OZ
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C80837
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459789-99-2
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Obeticholic acid
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9084
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SUB91981
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CHEMBL566315
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N0000192560
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PRIMARY | Farnesoid X Receptor Agonists [MoA] | ||
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100000141528
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TT-137
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0462Z4S4OZ
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447715
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CUMULATIVE EXCRETION |
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METABOLIC ENZYME->INHIBITOR OF EXPRESSION |
The effect of 10 mg OCA on CYP1A2 substrate caffeine showed that systemicexposure to caffeine increased by 42%. The systemic exposure to caffeine increased by 65% following 25 mg OCA.
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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TARGET -> AGONIST | |||
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CUMULATIVE EXCRETION |
Following an oral administration of 25 mg [14C]-OCA, about 87% of the dose is excreted in feces through biliary secretion. Less than 3% of the dose is excreted in the urine with no detection of OCA.
FECAL
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Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT |
AMOUNT ADMINISTERED
PLASMA
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
Related Record | Type | Details | ||
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IMPURITY -> PARENT |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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MULTIPLE ORAL ADMINISTRATION |
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