Maralixibat

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C40H56N3O4S
Molecular Weight	674.955
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 3
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

CCCCC1(CCCC)CS(=O)(=O)C2=C(C=C(C=C2)N(C)C)[C@H]([C@H]1O)C3=CC=C(OCC4=CC=C(C[N+]56CCN(CC5)CC6)C=C4)C=C3

InChI

InChIKey=STPKWKPURVSAJF-LJEWAXOPSA-N

InChI=1S/C40H56N3O4S/c1-5-7-19-40(20-8-6-2)30-48(45,46)37-18-15-34(41(3)4)27-36(37)38(39(40)44)33-13-16-35(17-14-33)47-29-32-11-9-31(10-12-32)28-43-24-21-42(22-25-43)23-26-43/h9-18,27,38-39,44H,5-8,19-26,28-30H2,1-4H3/q+1/t38-,39-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C40H55N3O4S
Molecular Weight	673.947
Charge	0
Count

Stereochemistry	EPIMERIC
Additional Stereochemistry	No
Defined Stereocenters	2 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214662s000lbl.pdf |https://pubmed.ncbi.nlm.nih.gov/34813049 | https://mirumpharma.com/#toggle-id-5

Maralixibat (Livmarli™) is a potent, apical, sodium‐dependent, bile acid transporter competitive inhibitor with minimal systemic absorption being developed by Mirum Pharmaceuticals for the treatment of rare cholestatic liver diseases including Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC) and biliary atresia. Maralixibat received its first approval on 29 September 2021, in the USA, for use in the treatment of cholestatic pruritus in patients with ALGS 1 year of age and older. Maralixibat is also under regulatory review for ALGS in Europe, and clinical development for cholestatic liver disorders including ALGS in patients under 1 year of age, PFIC and biliary atresia is continuing in several other countries. This article summarises the milestones in the development of maralixibat leading to this first approval for ALGS.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ileal bile acid transporter 5 Target ID: CHEMBL2778 Sources: https://www.ema.europa.eu/en/documents/withdrawal-report/withdrawal-assessment-report-livmarli_en.pdf \|https://pubmed.ncbi.nlm.nih.gov/30288474	Inhibitor 8504		0.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cholestatic pruritus in patients with Alagille syndrome 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214662s000lbl.pdf	Primary		Approved 8583	Livmarli Approved Use Treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 1 year of age and older. Launch Date 2021

C_max

Value	Dose	Analyte	Population
0.454 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.081 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
0.31 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
0.727 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
2.078 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
2.401 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
0.032 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.129 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.376 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.31 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.781 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.146 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.27 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.437 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
1.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.564 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
3.05 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Analyte	Population
0.946 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.161 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
0.6 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
1.668 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
7.51 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
14.191 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
0.032 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.248 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.152 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.424 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.614 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.24 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.514 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
3.07 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1.4 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
10.2 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Analyte	Population
2.023 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
3.791 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=191	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
1.275 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.367 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.282 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=195	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.61 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1.44 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1.97 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=198	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MARALIXIBAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2.7% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf3page=34 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=186			MARALIXIBAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 ug/kg/day 1 times / day multiple, oral Highest studied dose Dose: 400 ug/kg/day, 1 times / day Route: oral Route: multiple Dose: 400 ug/kg/day, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf	unhealthy, CHILD Health Status: unhealthy Age Group: CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf
400 ug/kg/day 2 times / day multiple, oral Highest studied dose Dose: 400 ug/kg/day, 2 times / day Route: oral Route: multiple Dose: 400 ug/kg/day, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf	unhealthy, CHILD Health Status: unhealthy Age Group: CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP2B1 157 OCTN2 71 BCRP 910 OCTN1 32 OCT3 159 MRP2 499 OATP1B1 1079	OATP1B3 435 P-gp 2052 OATP2B1 122 OATP1B1 503 BCRP 697	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	no
OATP2B1 162	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=35 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=205 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=209 Page: 35 \| 106 \| 187 \| 205 \| 207 \| 209	yes [IC50 1.02 uM]	no (co-administration study) Comment: Simvastatin, lovastatin or atorvastatin did not have a clinically relevant effect on the pharmacokinetics of these statins and their metabolites. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=35 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=205 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=209 Page: 35 \| 106 \| 187 \| 205 \| 207 \| 209
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=35 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 35 \| 105 \| 187	yes [IC50 10.9 uM]	weak (co-administration study) Comment: Clinically relevant effects on the pharmacokinetics of CYP3A4 substrates are expected to be minimal. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=35 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 35 \| 105 \| 187
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	yes [Inhibition 10 uM]
MRP2 625	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	yes [Inhibition 10 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	yes [Inhibition 10 uM]
OCT3 161	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	yes [Inhibition 10 uM]
OCTN1 32	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	yes [Inhibition 10 uM]
OCTN2 71	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=187 Page: 187.0	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=34 Page: 34 \| 187	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=34 Page: 34 \| 187	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=34 Page: 34 \| 187	no
OATP2B1 122	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=34 Page: 34 \| 187	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=34 Page: 34 \| 187	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214662Orig1s000IntegratedR.pdf#page=140 Page: 140.0

PubMed

Title	Date	PubMed
A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis.	2019-03	30859149
Placebo-Controlled Randomized Trial of an Intestinal Bile Salt Transport Inhibitor for Pruritus in Alagille Syndrome.	2018-10	30288474
A Drug Regimen for Progressive Familial Cholestasis Type 2.	2018-01	29284646

Sample Use Guides

In Vivo Use Guide

The recommended dosage is 380 mcg/kg once daily, taken 30 minutes before the first meal of the day.

Route of Administration: Oral

In Vitro Use Guide

In baby hamster kidney cells, maralixibat was shown to be a potent, competitive, and reversible inhibitor of the uptake of [14C]taurocholate by the ASBT (IC50 0.28±0.03nM). Maralixibat also inhibited [14C]alanine uptake via another cellular sodium-dependent cotransporter; however, the potency was markedly lower (IC50 35,700±3000nM). In transfected Chinese hamster ovary cells, maralixibat at 50uM produced a 5% inhibition of liver sodium taurocholate cotransporting polypeptide activity.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:11:52 GMT 2025` Edited by `admin` on `Mon Mar 31 22:11:52 GMT 2025`
Record UNII	UYB6UOF69L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LUM-001 CATION

Preferred Name

English

Maralixibat

Official Name

English

Maralixibat [WHO-DD]

Common Name

English

LOPIXIBAT

Common Name

English

TAK-625

Code

English

LUM001 CATION

Code

English

MARALIXIBAT [USAN]

Common Name

English

MARALIXIBAT CATION

Common Name

English

4-AZA-1-AZONIABICYCLO(2.2.2)OCTANE, 1-((4-((4-((4R,5R)-3,3-DIBUTYL-7-(DIMETHYLAMINO)-2,3,4,5-TETRAHYDRO-4-HYDROXY-1,1-DIOXIDO-1-BENZOTHIEPIN-5-YL)PHENOXY)METHYL)PHENYL)METHYL)-

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

406013