Details of the Drug

General Information of Drug (ID: DMJCF1O)

Drug Name

Maralixibat

Synonyms

Lopixibat; UNII-UYB6UOF69L; Maralixibat [USAN]; 716313-53-0; UYB6UOF69L; CHEMBL363392; Maralixibat (USAN); Lopixibat cation; CHEMBL17879; 1-(4-((4-((4R,5R)-3,3-dibutyl-7-(dimethylamino)-4-hydroxy-1,1-dioxido-2,3,4,5-tetrahydrobenzo[b]thiepin-5-yl)phenoxy)methyl)benzyl)-1,4-diazabicyclo[2.2.2]octan-1-ium; LUM001 CATION; LUM-001 CATION; SCHEMBL10013954; BDBM50140282; 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)-; D10951; Q27291331; (4R,5R)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2H-1$l^{6}-benzothiepin-4-ol; 1-{4-[4-((4R,5R)-3,3-Dibutyl-7-dimethylamino-4-hydroxy-1,1-dioxo-2,3,4,5-tetrahydro-1H-1lambda*6*-benzo[b]thiepin-5-yl)-phenoxymethyl]-benzyl}-4-aza-1-azonia-bicyclo[2.2.2]octane; chloride

Indication

Disease Entry	ICD 11	Status	REF
Progressive familial intrahepatic cholestasis	5C58.03	Phase 3	[1]
Alagille syndrome	LB20.0Y	Phase 2	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

675

Topological Polar Surface Area (xlogp)

7.1

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 3.43 +/- 2.13 mcgh/L [3]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1.65 +/- 1.10 mcg/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.75 h [3]
Elimination: A 5 mg radiolabelled dose of maralixibat is 73% eliminated in feces and 0.066% eliminated in urine [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 1.6 hours [3]

Chemical Identifiers

Formula: C40H56N3O4S+
IUPAC Name: (4R,5R)-5-[4-[[4-(4-aza-1-azoniabicyclo[2.2.2]octan-1-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2H-1lambda6-benzothiepin-4-ol
Canonical SMILES: CCCCC1(CS(=O)(=O)C2=C(C=C(C=C2)N(C)C)[C@H]([C@H]1O)C3=CC=C(C=C3)OCC4=CC=C(C=C4)C[N+]56CCN(CC5)CC6)CCCC
InChI: 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
InChIKey: STPKWKPURVSAJF-LJEWAXOPSA-N

Cross-matching ID

PubChem CID: 9831643
CAS Number: 716313-53-0
DrugBank ID: DB16226
TTD ID: DZB84T

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ileal sodium/bile acid cotransporter (SLC10A2)	TTPI1M5	NTCP2_HUMAN	Inhibitor	[4]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Progressive familial intrahepatic cholestasis

ICD Disease Classification

5C58.03

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Ileal sodium/bile acid cotransporter (SLC10A2)	DTT	SLC10A2	2.54E-01	-0.06	-0.17

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT04185363) An Extension Study of Maralixibat in Patients With Progressive Familial Intrahepatic Cholestasis (PFIC). U.S. National Institutes of Health.
2	ClinicalTrials.gov (NCT04729751) A Study to Evaluate the Safety and Tolerability of Maralixibat in Infant Participants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS). (RISE). U.S. National Institutes of Health.
3	FDA Approved Drug Products: Livmarli (Marilixibat) Oral Solution
4	Ileal bile acid transporter inhibition as an anticholestatic therapeutic target in biliary atresia and other cholestatic disorders. Hepatol Int. 2020 Sep;14(5):677-689.
5	Elobixibat for the treatment of constipation. Expert Opin Investig Drugs. 2013 Feb;22(2):277-84.
6	Current research on the treatment of primary sclerosing cholangitis. Intractable Rare Dis Res. 2015 Feb; 4(1): 1-6.
7	Inhibition of ileal Na+/bile acid cotransporter by S-8921 reduces serum cholesterol and prevents atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol. 1998 Aug;18(8):1304-11.
8	Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes. Am J Physiol Endocrinol Metab. 2012 Jan 1;302(1):E68-76.
9	Discovery of a highly potent, nonabsorbable apical sodium-dependent bile acid transporter inhibitor (GSK2330672) for treatment of type 2 diabetes. J Med Chem. 2013 Jun 27;56(12):5094-114.
10	Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol. 1998 Jan;274(1 Pt 1):G157-69.
11	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 960).