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

CC[C@H]1[C@@H](O)[C@H]2[C@@H]3CC[C@H]([C@H](C)CCC(O)=O)[C@@]3(C)CC[C@@H]2[C@@]4(C)CC[C@@H](O)C[C@@H]14

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 29 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 2752		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 8583	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) Health Status: unhealthy Age Group: 56 years (range: 29 - 86 years) Sex: M+F 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 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) Health Status: unhealthy Age Group: 56 years (range: 29 - 86 years) Sex: M+F 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 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 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 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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207999s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inducer 440 inhibitor 2438	inhibitor 2507 inducer 109	inducer 24

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057	BCRP 697 MRP2 252 MRP3 58 MRP4 91 BSEP 63 P-gp 2052 ASBT 5 NTCP 22 MATE1 182 MATE2 98 OATP1B1 503 OATP1B3 435 OAT1 395 OAT3 391 OCT1 393 OCT2 434	CYP1A2 832 CYP2B6 669 CYP2C8 198 CYP2C19 329 P-gp 301 BCRP 101 OATP1B1 29 OATP1B3 8 OCT2 5 BSEP 8 MRP2 146 MRP3 83 MRP4 53 ASBT 1 OCT1 39

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 2633	inhibitor 4027 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 1117	inhibitor 4027 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 1932	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >100 uM]
P-gp 1932	inducer 1966 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 1932	inducer 1966 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 782	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >30 uM]
OCT2 782	inducer 1966 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 782	inducer 1966 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 985	inducer 1966 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 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2B6 1160	inhibitor 4027 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 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2C8 1117	inhibitor 4027 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 2497	inhibitor 4027 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 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2D6 2546	inhibitor 4027 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 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no	Tauro-OCA 1
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2D6 2546	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2D6 2546	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2D6 2546	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no	Glyco-OCA 1
CYP2C19 2141	inhibitor 4027 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 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	unlikely [IC50 40 uM]
CYP2C19 2141	inhibitor 4027 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 554	inducer 1966 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 2497	inhibitor 4027 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 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 12 uM]
MRP2 625	inducer 1966 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 1160	inhibitor 4027 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 2333	inhibitor 4027 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 554	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 13.7 uM]
MRP4 345	inducer 1966 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 656	inducer 1966 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 326	inducer 1966 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 985	inducer 1966 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 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 15 uM]
CYP3A4 2633	inhibitor 4027 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 970	inducer 1966 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 1095	inducer 1966 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 970	inducer 1966 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 970	inducer 1966 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 625	inducer 1966 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 985	inducer 1966 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 8	inducer 1966 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 8	inducer 1966 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 1095	inducer 1966 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 656	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 30 uM]
CYP2D6 2546	inhibitor 4027 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 1095	inducer 1966 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 8	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 43.1 uM]
MRP4 345	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 45.6 uM]
MRP3 326	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 5.64 uM]
MRP3 326	inducer 1966 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 554	inducer 1966 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 345	inducer 1966 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 625	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 69.4 uM]
OCT1 656	inducer 1966 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 5	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
BSEP 63	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MATE2 98	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE2 98	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MATE2 98	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP2 252	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP2 252	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP2 252	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP3 58	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP3 58	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP3 58	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP4 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP4 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP4 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
NTCP 22	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	weak
ASBT 5	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
ASBT 5	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
BSEP 63	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
NTCP 22	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
NTCP 22	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OATP1B3 435	substrate 4014 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 2263	inducer 28 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
FXR protects lung from lipopolysaccharide-induced acute injury.	2012-01	22135065
Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease.	2011-04	21242261
The farnesoid X receptor FXRalpha/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution.	2007-09	17567710
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.	2005-10	15980055
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.	2005-08	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.	2005-08	15860571
Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis.	2005-05	15644430
6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity.	2002-08-15	12166927
Nuclear receptors and lipid physiology: opening the X-files.	2001-11-30	11729302
Identification of a nuclear receptor for bile acids.	1999-05-21	10334992

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

DSP-1747

Preferred Name

English

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

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