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

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

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 2637		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 8307	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 1.46430715E12

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 1532 inducer 753	inducer 372 inhibitor 1695	inhibitor 1789 inducer 97	inducer 23

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2B6 770 CYP2C8 869 CYP2C19 1410	BCRP 545 MRP2 196 MRP3 50 MRP4 75 BSEP 52 P-gp 1491 ASBT 3 NTCP 16 MATE1 131 MATE2 93 OATP1B1 389 OATP1B3 333 OAT1 314 OAT3 328 OCT1 317 OCT2 336	CYP1A2 671 CYP2B6 521 CYP2C8 163 CYP2C19 283 P-gp 252 BCRP 74 OATP1B1 26 OATP1B3 6 OCT2 5 BSEP 6 MRP2 108 MRP3 53 MRP4 31 ASBT 1 OCT1 19

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1857	inhibitor 3185 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 923	inhibitor 3185 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 1588	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >100 uM]
P-gp 1588	inducer 1515 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 1588	inducer 1515 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 631	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	no [IC50 >30 uM]
OCT2 631	inducer 1515 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 631	inducer 1515 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 751	inducer 1515 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 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2B6 946	inhibitor 3185 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 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2C8 923	inhibitor 3185 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 1747	inhibitor 3185 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 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no [IC50 >50 uM]
CYP2D6 1826	inhibitor 3185 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 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP1A2 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP1A2 1620	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no	Tauro-OCA 1
CYP2B6 946	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2B6 946	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2B6 946	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C19 1484	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C19 1484	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C19 1484	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C8 923	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C8 923	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C8 923	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2C9 1747	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2C9 1747	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2C9 1747	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP2D6 1826	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP2D6 1826	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP2D6 1826	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP3A4 1857	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no
CYP3A4 1857	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Glyco-OCA 1
CYP3A4 1857	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=76 Page: 76.0	no	Tauro-OCA 1
CYP3A4 1857	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	no	Glyco-OCA 1
CYP2C19 1484	inhibitor 3185 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 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	unlikely [IC50 40 uM]
CYP2C19 1484	inhibitor 3185 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 393	inducer 1515 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 1747	inhibitor 3185 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 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 12 uM]
MRP2 452	inducer 1515 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 946	inhibitor 3185 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 1620	inhibitor 3185 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 393	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 13.7 uM]
MRP4 235	inducer 1515 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 513	inducer 1515 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 206	inducer 1515 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 751	inducer 1515 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 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=74 Page: 74.0	yes [IC50 15 uM]
CYP3A4 1857	inhibitor 3185 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 700	inducer 1515 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 785	inducer 1515 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 700	inducer 1515 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 700	inducer 1515 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 452	inducer 1515 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 751	inducer 1515 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 1515 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 1515 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 785	inducer 1515 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 513	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 30 uM]
CYP2D6 1826	inhibitor 3185 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 785	inducer 1515 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 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 43.1 uM]
MRP4 235	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 45.6 uM]
MRP3 206	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 5.64 uM]
MRP3 206	inducer 1515 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 393	inducer 1515 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 235	inducer 1515 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 452	inducer 1515 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=83 Page: 83.0	yes [IC50 69.4 uM]
OCT1 513	inducer 1515 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 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
BCRP 545	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
BCRP 545	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
BCRP 545	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
BSEP 52	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE1 131	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE1 131	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MATE1 131	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MATE2 93	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MATE2 93	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MATE2 93	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP2 196	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP2 196	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP2 196	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP3 50	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP3 50	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP3 50	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
MRP4 75	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
MRP4 75	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
MRP4 75	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
NTCP 16	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OAT1 314	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OAT1 314	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OAT1 314	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
OAT3 328	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OATP1B1 389	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OATP1B3 333	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT1 317	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT1 317	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OCT1 317	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
OCT2 336	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no
OCT2 336	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Glyco-OCA 1
OCT2 336	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	no	Tauro-OCA 1
P-gp 1491	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	weak
ASBT 3	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
ASBT 3	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
BSEP 52	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
NTCP 16	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
NTCP 16	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OAT3 328	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OAT3 328	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OATP1B1 389	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OATP1B1 389	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Tauro-OCA 1
OATP1B3 333	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/207999Orig1s000ClinPharmR.pdf#page=82 Page: 82.0	yes	Glyco-OCA 1
OATP1B3 333	substrate 3264 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 1603	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
6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity.	2002 Aug 15	12166927
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
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 22:01:48 UTC 2022` Edited by `admin` on `Fri Dec 16 22:01:48 UTC 2022`
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

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

FDA ORPHAN DRUG

259008