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

Structure Search

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000Lbl.pdf | http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100153/ocaliva-obeticholic-acid

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 Target ID: CHEMBL2047 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000Lbl.pdf \| http://interceptpharma.com/wp-content/themes/intercept/pdf/Intercept_Company_Presentation.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/12166927	Agonist 2678		0.09 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Primary biliary cholangitis 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000Lbl.pdf	Primary		Approved 8429	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 2016

C_max

Value	Dose	Co-administered	Analyte	Population
68.3 ng/mL OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/ocaliva-epar-public-assessment-report_en.pdf	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 OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/ocaliva-epar-public-assessment-report_en.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207999s003lbl.pdf			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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	Disc. AE: Pruritus... AEs leading to discontinuation/dose reduction: Pruritus (10%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	Other AEs: Ascites, Jaundice... Other AEs: Ascites Jaundice Portal hypertension Primary biliary cholangitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf

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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf	unhealthy Health Status: unhealthy Condition: primary biliary cholangitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inducer 389 inhibitor 1767	inhibitor 1852 inducer 97	inducer 23

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C8 911 CYP2C19 1478	BCRP 561 MRP2 205 MRP3 50 MRP4 77 BSEP 52 P-gp 1537 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

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 44 uM]	Tauro-OCA 1
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 9.2 uM]	Glyco-OCA 1
P-gp 1650	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >100 uM]
P-gp 1650	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >100 uM]	Glyco-OCA 1
P-gp 1650	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >100 uM]	Tauro-OCA 1
OCT2 648	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >30 uM]
OCT2 648	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >30 uM]	Glyco-OCA 1
OCT2 648	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >30 uM]	Tauro-OCA 1
BCRP 773	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >300 uM]	Glyco-OCA 1	no (co-administration study) Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]	Glyco-OCA 1
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]	Tauro-OCA 1
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]	Glyco-OCA 1
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]	Tauro-OCA 1
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no	Tauro-OCA 1
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2D6 1891	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2D6 1891	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2D6 1891	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no	Glyco-OCA 1
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no	Glyco-OCA 1	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	unlikely [IC50 40 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	unlikely [IC50 50 uM]	Tauro-OCA 1
BSEP 403	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 10.5 uM]	Tauro-OCA 1
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 11 uM]	Tauro-OCA 1	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 12 uM]
MRP2 475	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 126 uM]	Glyco-OCA 1
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 13 uM]	Tauro-OCA 1
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 13 uM]	Glyco-OCA 1	yes (co-administration study) Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of caffeine increased by 65% and 10%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0
BSEP 403	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 13.7 uM]
MRP4 238	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 131 uM]	Tauro-OCA 1
OCT1 543	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 138 uM]	Tauro-OCA 1
MRP3 207	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 14.6 uM]	Glyco-OCA 1
BCRP 773	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 146 uM]	Tauro-OCA 1	no (co-administration study) Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 15 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0
OATP1B3 715	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
OATP1B1 803	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
OATP1B3 715	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 2.93 uM]	Glyco-OCA 1	no (co-administration study) Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
OATP1B3 715	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 2.95 uM]	Tauro-OCA 1	no (co-administration study) Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
MRP2 475	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 205 uM]	Tauro-OCA 1
BCRP 773	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
ASBT 6	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 21.5 uM]	Tauro-OCA 1
ASBT 6	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 27.2 uM]	Glyco-OCA 1
OATP1B1 803	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 3.01 uM]	Tauro-OCA 1	no (co-administration study) Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
OCT1 543	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 30 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 35 uM]	Glyco-OCA 1	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0
OATP1B1 803	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 4.05 uM]	Glyco-OCA 1	no (co-administration study) Comment: Following multiple doses of OCA 25 mg QD, AUCinf and Cmax of RSV increased by 30% and 26%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0
ASBT 6	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 43.1 uM]
MRP4 238	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 45.6 uM]
MRP3 207	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 5.64 uM]
MRP3 207	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 51 uM]	Tauro-OCA 1
BSEP 403	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 6.9 uM]	Glyco-OCA 1
MRP4 238	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 68.5 uM]	Glyco-OCA 1
MRP2 475	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 69.4 uM]
OCT1 543	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 93.3 uM]	Glyco-OCA 1

Drug as victim

Target	Modality	Activity	Metabolite
ASBT 3	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP3 50	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP3 50	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP3 50	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP4 77	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP4 77	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP4 77	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
NTCP 17	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	weak
ASBT 3	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
ASBT 3	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
NTCP 17	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
NTCP 17	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inducer 27 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000PharmR.pdf#page=32 Page: 32.0

Sourcing

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

PubMed

Title	Date	PubMed
Nuclear receptors and lipid physiology: opening the X-files.	2001 Nov 30	11729302
6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity.	2002 Aug 15	12166927
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	15911693
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	15860571
Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis.	2005 May	15644430
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	15980055
The farnesoid X receptor FXRalpha/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution.	2007 Sep	17567710
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

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.

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

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

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

NDF-RT

N0000192561