U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C26H44O4
Molecular Weight 420.6261
Optical Activity UNSPECIFIED
Defined Stereocenters 11 / 11
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OBETICHOLIC ACID

SMILES

CC[C@]1([H])[C@]2([H])C[C@@]([H])(CC[C@]2(C)[C@@]3([H])CC[C@]4(C)[C@]([H])(CC[C@@]4([H])[C@]3([H])[C@]1([H])O)[C@]([H])(C)CCC(=O)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

HIDE SMILES / InChI

Molecular Formula C26H44O4
Molecular Weight 420.6261
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 11 / 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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
OCALIVA

Approved Use

OCALIVA, 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 Date

1464307200000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
OBETICHOLIC ACID plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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)
Health Status: unhealthy
Age Group: 56 years (range: 29 - 86 years)
Sex: M+F
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
Other AEs: Ascites, Jaundice...
Other AEs:
Ascites
Jaundice
Portal hypertension
Primary biliary cholangitis
Sources:
AEs

AEs

AESignificanceDosePopulation
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)
Health Status: unhealthy
Age Group: 56 years (range: 29 - 86 years)
Sex: M+F
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
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
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
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
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 44 uM]
no [IC50 9.2 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >300 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of omeprazole increased by 36% and 15%, respectively (Table 37). AUCinf and Cmax of 5-hydroxy-omeprazole increased by about 18% and 3.4%, respectively
Page: 74
unlikely [IC50 40 uM]
unlikely [IC50 50 uM]
yes [IC50 10.5 uM]
yes [IC50 11 uM]
no (co-administration study)
Comment: Although the systemic exposure of S-warfarin was increased following multiple doses of OCA 10 or 25 mg QD, the INR changes were <10% except the Emax change, which was only 1.1% more than 10%, following 10 mg dose
Page: 74
yes [IC50 12 uM]
yes [IC50 126 uM]
yes [IC50 13 uM]
yes [IC50 13 uM]
yes (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of caffeine increased by 65% and 10%, respectively
Page: 74
yes [IC50 13.7 uM]
yes [IC50 131 uM]
yes [IC50 138 uM]
yes [IC50 14.6 uM]
yes [IC50 146 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
yes [IC50 15 uM]
yes [IC50 19 uM]
no (co-administration study)
Comment: following multiple doses of OCA 25 mg QD, AUCinf and Cmax of midazolam increased by 26% and 17%, respectively
Page: 74
yes [IC50 2.15 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
yes [IC50 2.57 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
yes [IC50 2.93 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
yes [IC50 2.95 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
yes [IC50 205 uM]
yes [IC50 21.1 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
yes [IC50 21.5 uM]
yes [IC50 27.2 uM]
yes [IC50 3.01 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
yes [IC50 30 uM]
yes [IC50 35 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of DXM decreased by 11% and 17.4%, respectively
Page: 74
yes [IC50 4.05 uM]
no (co-administration study)
Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively
Page: 83
yes [IC50 43.1 uM]
yes [IC50 45.6 uM]
yes [IC50 5.64 uM]
yes [IC50 51 uM]
yes [IC50 6.9 uM]
yes [IC50 68.5 uM]
yes [IC50 69.4 uM]
yes [IC50 93.3 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
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

Patents

Sample Use Guides

Starting Dosage: The recommended starting dosage of OCALIVA is 5
Route of Administration: Oral
In HuH7 cells, Obeticholic Acid acts as a potent FXR agonist with EC50 of 85 nM.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:37:00 UTC 2021
Edited
by admin
on Fri Jun 25 21:37:00 UTC 2021
Record UNII
0462Z4S4OZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OBETICHOLIC ACID
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
(3.ALPHA.,5.BETA.,6.ALPHA.,7.ALPHA.)-6-ETHYL-3,7-DIHYDROXYCHOLAN-24-OIC ACID
Common Name English
OBETICHOLIC ACID [INN]
Common Name English
DSP-1747
Code English
OCALIVA
Common Name English
INT-747
Code English
6-ETHYLCHENODEOXYCHOLIC ACID
Common Name English
OBETICHOLIC ACID [JAN]
Common Name English
OBETICHOLIC ACID [MI]
Common Name English
6-ECDCA
Common Name English
OBETICHOLIC ACID [WHO-DD]
Common Name English
CHOLAN-24-OIC ACID, 6-ETHYL-3,7-DIHYDROXY-, (3.ALPHA.,5.BETA.,6.ALPHA.,7.ALPHA.)-
Common Name English
OBETICHOLIC ACID [USAN]
Common Name English
OBETICHOLIC ACID [ORANGE BOOK]
Common Name English
6-ALPHA-ETHYLCHENODEOXYCHOLIC ACID
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 259008
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
NDF-RT N0000192561
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
NCI_THESAURUS C1636
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
EU-Orphan Drug EU/3/10/753
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
FDA ORPHAN DRUG 253207
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
WHO-ATC A05AA04
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
Code System Code Type Description
EPA CompTox
459789-99-2
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
DRUG CENTRAL
5155
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
RXCUI
1798288
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
MERCK INDEX
M11955
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
DRUG BANK
DB05990
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
FDA UNII
0462Z4S4OZ
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
NCI_THESAURUS
C80837
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
CAS
459789-99-2
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
INN
9084
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
EVMPD
SUB91981
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
ChEMBL
CHEMBL566315
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
NDF-RT
N0000192560
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY Farnesoid X Receptor Agonists [MoA]
PUBCHEM
447715
Created by admin on Fri Jun 25 21:37:00 UTC 2021 , Edited by admin on Fri Jun 25 21:37:00 UTC 2021
PRIMARY
Related Record Type Details
CUMULATIVE EXCRETION
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.
TARGET -> INHIBITOR
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
TARGET -> AGONIST
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
Related Record Type Details
METABOLITE ACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
AMOUNT ADMINISTERED
PLASMA
METABOLITE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC MULTIPLE ORAL ADMINISTRATION

ONCE DAILY DOSE