OBETICHOLIC ACID

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

HIDE SMILES / InChI

Molecular Formula	C26H44O4
Molecular Weight	420.6252
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 11
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

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
Bile acid receptor FXR 31	Agonist 2,678		0.09 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Primary biliary cholangitis 1	Primary		Approved 8,429	OCALIVA

C_max

Value	Dose	Co-administered	Analyte	Population
68.3 ng/mL	10 mg single, oral		OBETICHOLIC ACID plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
747 ng × h/mL	10 mg single, oral		OBETICHOLIC ACID plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1%			OBETICHOLIC ACID plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
10 mg 1 times / day multiple, oral	unhealthy, 56 years (range: 29 - 86 years) n = 73	Disc. AE: Pruritus...
50 mg 1 times / day multiple, oral Overdose	unhealthy	Other AEs: Ascites, Jaundice...

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AEs

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AE	Significance	Dose	Population
Pruritus	10% Disc. AE	10 mg 1 times / day multiple, oral	unhealthy, 56 years (range: 29 - 86 years) n = 73
Ascites		50 mg 1 times / day multiple, oral Overdose	unhealthy
Jaundice		50 mg 1 times / day multiple, oral Overdose	unhealthy
Portal hypertension		50 mg 1 times / day multiple, oral Overdose	unhealthy
Primary biliary cholangitis		50 mg 1 times / day multiple, oral Overdose	unhealthy

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587 inducer 781	inducer 389 inhibitor 1,767	inhibitor 1,852 inducer 97	inducer 23

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2B6 810 CYP2C8 911 CYP2C19 1,478	BCRP 561 MRP2 205 MRP3 50 MRP4 77 BSEP 52 P-gp 1,537 ASBT 3 NTCP 17 MATE1 135 MATE2 96 OATP1B1 406 OATP1B3 350 OAT1 326 OAT3 339 OCT1 327 OCT2 355	CYP1A2 701 CYP2B6 547 CYP2C8 168 CYP2C19 293 P-gp 257 BCRP 75 OATP1B1 26 OATP1B3 6 OCT2 6 BSEP 6 MRP2 111 MRP3 53 MRP4 32 ASBT 1 OCT1 35

Drug as perpetrator

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Target	Modality	Activity	Metabolite
CYP3A4 1,925	inhibitor 3,277	no [IC50 44 uM]	Tauro-OCA 1
CYP2C8 965	inhibitor 3,277	no [IC50 9.2 uM]	Glyco-OCA 1
P-gp 1,650	inducer 1,573	no [IC50 >100 uM]
P-gp 1,650	inducer 1,573	no [IC50 >100 uM]	Glyco-OCA 1
P-gp 1,650	inducer 1,573	no [IC50 >100 uM]	Tauro-OCA 1

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Drug as victim

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Target	Modality	Activity	Metabolite
ASBT 3	substrate 3,367	no
BCRP 561	substrate 3,367	no
BCRP 561	substrate 3,367	no	Glyco-OCA 1
BCRP 561	substrate 3,367	no	Tauro-OCA 1
BSEP 52	substrate 3,367	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inducer 27

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:43602	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:43602
MolPort	MolPort-035-682-579	https://www.molport.com/shop/molecule-link/MolPort-035-682-579
ZINC	ZINC000014164617	http://zinc15.docking.org/substances/ZINC000014164617

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PubMed

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Title	Date	PubMed
6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity.	2002 Aug 15	12166927
Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease.	2011 Apr	21242261
FXR protects lung from lipopolysaccharide-induced acute injury.	2012 Jan	22135065

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Patents

Sample Use Guides

In Vivo Use Guide

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

In HuH7 cells, Obeticholic Acid acts as a potent FXR agonist with EC50 of 85 nM.

Substance Class	Chemical
Record UNII	0462Z4S4OZ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

OBETICHOLIC ACID

Official Name

English

Obeticholic acid [WHO-DD]

Common 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

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Classification Tree

Code System

Code

Established Pharmacologic Class

NDF-RT

N0000192561

Therapeutic Hormone

NCI_THESAURUS

C1636

Positive

EU-Orphan Drug

EU/3/10/753

Designated/Approved

FDA ORPHAN DRUG

253207

Designated/Withdrawn

FDA ORPHAN DRUG

259008

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Code System

Code

Type

Description

CHEBI

43602

PRIMARY

EPA CompTox

DTXSID20196671

PRIMARY

DRUG CENTRAL

5155

PRIMARY

RXCUI

1798288

PRIMARY

MERCK INDEX

m11955

PRIMARY

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Related Record

Type

Details


					0462Z4S4OZ

OBETICHOLIC ACID

CUMULATIVE EXCRETION

Amount:

MOLE PERCENT OF AMOUNT ADMINISTERED 3 % (average)


					VK4SQL11C0

CYTOCHROME P450 1A2

METABOLIC ENZYME->INHIBITOR OF EXPRESSION

Comments:

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.


					PG6GA793XH

RETINOID X RECEPTOR ALPHA

TARGET -> INHIBITOR


					2PDN1S3FVX

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA

TARGET -> INHIBITOR


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

[>99] % (average)

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Related Record

Type

Details


					T5IG4XE90K

TAURO-OBETICHOLIC ACID

METABOLITE ACTIVE -> PARENT


					O2MZK6V9LQ

GLYCO-OBETICHOLIC ACID

METABOLITE ACTIVE -> PARENT

Interaction Type:

AMOUNT ADMINISTERED

Qualification:

PLASMA

Amount:

47.4 % (average)


					MX5RXA86QQ

OBETICHOLIC ACID 3-GLUCURONIDE

METABOLITE -> PARENT


					Y62YER47AU

OBETICHOLIC ACID 24-GLUCURONIDE

METABOLITE -> PARENT

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Related Record

Type

Details


					4V5HIB7ESR

7-EPI-OBETICHOLIC ACID 3-OBETICHOLATE ESTER

IMPURITY -> PARENT

Amount:

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Related Record

Type

Details


					0462Z4S4OZ

OBETICHOLIC ACID

ACTIVE MOIETY

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Name	Property Type	Amount	Parameters
Biological Half-life	PHARMACOKINETIC	24 hours (average)

Volume of Distribution	PHARMACOKINETIC	8.83 Liters/Kilogram (average)

Tmax	PHARMACOKINETIC	1.5 hours (average)	MULTIPLE ORAL ADMINISTRATION ONCE DAILY DOSE 10 mg (average)

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

F_unbound

Drug as perpetrator