Details of the Drug

General Information of Drug (ID: DMYN391)

• Drug Name: Odevixibat
• Synonyms: 501692-44-0; UNII-2W150K0UUC; 2W150K0UUC; A4250; AZD8294; 501692-44-0 (free base); Odevixibat (USAN); Odevixibat [USAN]; AR-H064974; A-4250; (S)-2-((R)-2-(2-((3,3-Dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydrobenzo[f][1,2,5]thiadiazepin-8-yl)oxy)acetamido)-2-(4-hydroxyphenyl)acetamido)butanoic acid; SCHEMBL946468; CHEMBL4297588; BDBM77040; GTPL11194; AZD-8294; example 5 [US9694018B1]; WHO 10706; HY-109120; Unk-D-nTyr-Abu-OH (IUPAC condensed name); CS-0078340; D11716; US9694018, 5; (2S)-2-(((2R)-2-((((3,3-Dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro- 1,2,5-benzothiadiazepin-8-yl)oxy)acetyl)amino)-2-(4-hydroxyphenyl)acetyl)amino)butanoic acid; (2S)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]butanoic acid; Butanoic acid, 2-(((2R)-((((3,3-dibutyl-2,3,4,5-tetrahydro-7-(methylthio)-1,1-dioxido-5-phenyl-1,2,5-benzothiadiazepin-8-yl)oxy)acetyl)amino)(4-hydroxyphenyl)acetyl)amino)-, (2S)-; Butanoic acid, 2-(((2R)-2-((2-((3,3-dibutyl-2,3,4,5-tetrahydro-7-(methylthio)-1,1-dioxido-5-phenyl-1,2,5-benzothiadiazepin-8-yl)oxy)acetyl)amino)-2-(4-hydroxyphenyl)acetyl)amino)-, (2S)-

Indication

Disease Entry	ICD 11	Status	REF
Alagille syndrome	LB20.0Y	Phase 3	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 4:
  Molecular Weight (mw); 740.9
  Topological Polar Surface Area (xlogp); 6.8
  Rotatable Bond Count (rotbonds); 17
  Hydrogen Bond Donor Count (hbonddonor); 5
  Hydrogen Bond Acceptor Count (hbondacc); 11
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 2.19 mcgh/L [2]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 0.47 mcg/L [2]
  Elimination: Odevixibat is 82.9% recovered in the feces and only less than 0.002% recovered in the urine [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.36 hours [2]
  Metabolism: The drug is metabolized via the mono-hydroxylation [2]
• Chemical Identifiers:
  Formula: C37H48N4O8S2
  IUPAC Name: (2S)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]butanoic acid
  Canonical SMILES: CCCCC1(CN(C2=CC(=C(C=C2S(=O)(=O)N1)OCC(=O)N[C@H](C3=CC=C(C=C3)O)C(=O)N[C@@H](CC)C(=O)O)SC)C4=CC=CC=C4)CCCC
  InChI: InChI=1S/C37H48N4O8S2/c1-5-8-19-37(20-9-6-2)24-41(26-13-11-10-12-14-26)29-21-31(50-4)30(22-32(29)51(47,48)40-37)49-23-33(43)39-34(25-15-17-27(42)18-16-25)35(44)38-28(7-3)36(45)46/h10-18,21-22,28,34,40,42H,5-9,19-20,23-24H2,1-4H3,(H,38,44)(H,39,43)(H,45,46)/t28-,34+/m0/s1
  InChIKey: XULSCZPZVQIMFM-IPZQJPLYSA-N
• Cross-matching ID:
  PubChem CID: 10153627
  CAS Number: 501692-44-0
  DrugBank ID: DB16261
  TTD ID: DEWC27

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	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Alagille syndrome
• ICD Disease Classification: LB20.0Y

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

References

• [1] ClinicalTrials.gov (NCT04674761) Efficacy and Safety of Odevixibat in Patients With Alagille Syndrome (ASSERT). U.S. National Institutes of Health.
• [2] FDA Approved Drug Products: Bylvay (Odevixibat) Oral Capsule
• [3] 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.
• [4] Elobixibat for the treatment of constipation. Expert Opin Investig Drugs. 2013 Feb;22(2):277-84.
• [5] Current research on the treatment of primary sclerosing cholangitis. Intractable Rare Dis Res. 2015 Feb; 4(1): 1-6.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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).