Details of the Drug

General Information of Drug (ID: DM3C9NV)

• Drug Name: TD-8954
• Synonyms: TD-8954; UNII-35F0Y2W16Q; CHEMBL2402904; 35F0Y2W16Q; 916075-84-8; compound 18 [PMID 23756062]; SCHEMBL390795; GTPL8426; BDBM50436989; SB17471; DB12725; 1-Piperidinecarboxylic acid, 4-((4-((((2-(1-methylethyl)-1H-benzimidazol-7-yl)carbonyl)amino)methyl)-1-piperidinyl)methyl)-, methyl ester; methyl 4-[[4-[[(2-propan-2-yl1H-benzimidazole-4-carbonyl)amino]methyl]piperidin-1-yl]methyl]piperidine-1-carboxylate

Indication

Disease Entry	ICD 11	Status	REF
Gastrointestinal disease	DE2Z	Phase 2	[1]
Alzheimer disease	8A20	Phase 1/2	[2], [3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 455.6
  Topological Polar Surface Area (xlogp); 3.4
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C25H37N5O3
  IUPAC Name: methyl 4-[[4-[[(2-propan-2-yl-1H-benzimidazole-4-carbonyl)amino]methyl]piperidin-1-yl]methyl]piperidine-1-carboxylate
  Canonical SMILES: CC(C)C1=NC2=C(C=CC=C2N1)C(=O)NCC3CCN(CC3)CC4CCN(CC4)C(=O)OC
  InChI: InChI=1S/C25H37N5O3/c1-17(2)23-27-21-6-4-5-20(22(21)28-23)24(31)26-15-18-7-11-29(12-8-18)16-19-9-13-30(14-10-19)25(32)33-3/h4-6,17-19H,7-16H2,1-3H3,(H,26,31)(H,27,28)
  InChIKey: MZOITCJKGUIQEI-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 11961293
  CAS Number: 916075-84-8
  DrugBank ID: DB12725
  TTD ID: D01HVZ

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	Modulator	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Gastrointestinal disease
• ICD Disease Classification: DE2Z

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] ClinicalTrials.gov (NCT03827655) A Study of TAK-954 to Treat Gastrointestinal Dysfunction in Adults After Surgery. U.S. National Institutes of Health.
• [2] 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. (Ligand id: 8426).
• [3] ClinicalTrials.gov (NCT01953081) A Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of a Single Dose of Intravenous TD-8954 Compared With Metoclopramide in Critically Ill Patients With Enteral Feeding Intolerance. U.S. National Institutes of Health.
• [4] 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.
• [5] 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.
• [6] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [7] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility. Aliment Pharmacol Ther. 1995 Oct;9(5):563-9.
• [12] 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.