Details of the Drug

General Information of Drug (ID: DM8BHL6)

• Drug Name: Naronapride
• Synonyms: Naronapride dihydrochloride; ATI-7500; ATI-7505; Cisapride analog, ARYx Therapeutics; ATI-7000 series, ARYx Therapeutics; Cisapride analog, Procter & Gamble; ATI-7000 series, Procter & Gamble; 5-HT 4 receptor agonist (oral, gastroesophageal reflux/irritable bowel syndrome/gastric motilitydisorder/constipation/dyspepsia), ARYx Therapeutics/Procter & Gamble Pharmaceuticals Inc

Indication

Disease Entry	ICD 11	Status	REF
Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 537.1
  Topological Polar Surface Area (xlogp); 2.8
  Rotatable Bond Count (rotbonds); 12
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C27H41ClN4O5
  IUPAC Name: [(3R)-1-azabicyclo[2.2.2]octan-3-yl] 6-[(3S,4R)-4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxypiperidin-1-yl]hexanoate
  Canonical SMILES: CO[C@H]1CN(CC[C@H]1NC(=O)C2=CC(=C(C=C2OC)N)Cl)CCCCCC(=O)O[C@H]3CN4CCC3CC4
  InChI: InChI=1S/C27H41ClN4O5/c1-35-23-15-21(29)20(28)14-19(23)27(34)30-22-9-13-31(17-25(22)36-2)10-5-3-4-6-26(33)37-24-16-32-11-7-18(24)8-12-32/h14-15,18,22,24-25H,3-13,16-17,29H2,1-2H3,(H,30,34)/t22-,24+,25+/m1/s1
  InChIKey: VGDDOIZXGFJDRC-VJTSUQJLSA-N
• Cross-matching ID:
  PubChem CID: 11237985
  CAS Number: 860174-12-5
  DrugBank ID: DB05542
  TTD ID: D08HGY

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 4 receptor (HTR4)	TT07C3Y	5HT4R_HUMAN	Agonist	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Gastroesophageal reflux disease
• ICD Disease Classification: DA22.Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
5-HT 4 receptor (HTR4)	DTT	HTR4	6.16E-01	-0.03	-0.24

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019926)
• [2] Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012 Apr;35(7):745-67.
• [3] Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5... Endocr Relat Cancer. 2009 Mar;16(1):281-90.
• [4] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [5] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [6] 5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist. J Vet Pharmacol Ther. 2002 Feb;25(1):49-58.
• [7] The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):125-37.
• [8] Pharmacology and metabolism of renzapride : a novel therapeutic agent for the potential treatment of irritable bowel syndrome. Drugs R D. 2008;9(1):37-63.
• [9] The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility. Aliment Pharmacol Ther. 1995 Oct;9(5):563-9.
• [10] The Pharmacology of TD-8954, a Potent and Selective 5-HT(4) Receptor Agonist with Gastrointestinal Prokinetic Properties. Front Pharmacol. 2011 May 30;2:25.
• [11] A randomized trial of 5-hydroxytryptamine4-receptor agonist, YKP10811, on colonic transit and bowel function in functional constipation. Clin Gastroenterol Hepatol. 2015 Apr;13(4):701-8.e1.