Details of the Drug

General Information of Drug (ID: DMRJ9P4)

• Drug Name: INT-767
• Synonyms: INT-767 sodium; 1000403-03-1 (sodium); 1000403-03-1; sodium (R)-3-((3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)butyl sulfate; CS-5007; HY-12434; Sulfuric acid sodium 3alpha,7alpha-dihydroxy-6alpha-ethyl-24-nor-5beta-cholane-23-yl ester salt

Indication

Disease Entry	ICD 11	Status	REF
Hepatic fibrosis	DB93.0	Preclinical	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 494.7
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 6
  Hydrogen Bond Donor Count; 2
  Hydrogen Bond Acceptor Count; 6
• Chemical Identifiers:
  Formula: C25H43NaO6S
  IUPAC Name: sodium;[(3R)-3-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]butyl] sulfate
  Canonical SMILES: CC[C@@H]1[C@@H]2C[C@@H](CC[C@@]2([C@H]3CC[C@]4([C@H]([C@@H]3[C@@H]1O)CC[C@@H]4[C@H](C)CCOS(=O)(=O)[O-])C)C)O.[Na+]
  InChI: InChI=1S/C25H44O6S.Na/c1-5-17-21-14-16(26)8-11-25(21,4)20-9-12-24(3)18(6-7-19(24)22(20)23(17)27)15(2)10-13-31-32(28,29)30;/h15-23,26-27H,5-14H2,1-4H3,(H,28,29,30);/q;+1/p-1/t15-,16-,17-,18-,19+,20+,21+,22+,23-,24-,25-;/m1./s1
  InChIKey: TXIWHUPIUUZFFK-PMWRKVJASA-M
• Cross-matching ID:
  PubChem CID: 23712772
  TTD ID: DNZ96J

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Farnesoid X-activated receptor (FXR)	TTS4UGC	NR1H4_HUMAN	Agonist	[2]
G-protein coupled bile acid receptor 1 (GPBAR1)	TTSDVTR	GPBAR_HUMAN	Agonist	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hepatic fibrosis
• ICD Disease Classification: DB93.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
G-protein coupled bile acid receptor 1 (GPBAR1)	DTT	GPBAR1	4.60E-01	0.02	0.09
Farnesoid X-activated receptor (FXR)	DTT	NR1H4	5.72E-01	0.39	1.68

References

• [1] Clinical pipeline report, company report or official report of Intercept.
• [2] FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity. J Am Soc Nephrol. 2018 Jan;29(1):118-137.
• [3] Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J Biol Chem. 2002 Aug 30;277(35):31441-7.
• [4] Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. J Nat Prod. 2009 Jan;72(1):24-8.
• [5] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [6] The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis. Hepatology. 2019 Sep;70(3):788-801.
• [7] The nuclear receptors FXR and LXRalpha: potential targets for the development of drugs affecting lipid metabolism and neoplastic diseases. Curr Pharm Des. 2001 Mar;7(4):231-59.
• [8] FXR modulators for enterohepatic and metabolic diseases.Expert Opin Ther Pat. 2018 Nov;28(11):765-782.
• [9] Clinical pipeline report, company report or official report of ENYO Pharma.
• [10] A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction. Liver Int. 2020 Jul;40(7):1655-1669.
• [11] Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2020 Apr 23;63(8):3868-3880.
• [12] Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism.Acta Pharmaceutica Sinica B Volume 5, Issue 2, March 2015, Pages 151-157.
• [13] Farnesoid X receptor modulators 2014-present: a patent review.Expert Opin Ther Pat. 2018 May;28(5):351-364.
• [14] Clinical pipeline report, company report or official report of Exelixis (2011).
• [15] 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: 37).
• [16] Synthesis and SAR of 2-aryl-3-aminomethylquinolines as agonists of the bile acid receptor TGR5. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5718-21.