velusetrag   Click here for help

GtoPdb Ligand ID: 8425

Synonyms: compound 15 [PMID 22959244] | TD-5108
Compound class: Synthetic organic
Comment: Velusetrag is a potent and selective, orally available agonist of the 5-HT4 receptor. The compound is being investigated as a treatment for chronic constipation [6,8] and irritable bowel syndrome [7].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 120.33
Molecular weight 504.24
XLogP 2.68
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES OC(CN(S(=O)(=O)C)C)CN1C2CCC1CC(C2)NC(=O)c1cc2ccccc2n(c1=O)C(C)C
Isomeric SMILES O[C@@H](CN(S(=O)(=O)C)C)CN1[C@@H]2CC[C@H]1CC(C2)NC(=O)c1cc2ccccc2n(c1=O)C(C)C
InChI InChI=1S/C25H36N4O5S/c1-16(2)29-23-8-6-5-7-17(23)11-22(25(29)32)24(31)26-18-12-19-9-10-20(13-18)28(19)15-21(30)14-27(3)35(4,33)34/h5-8,11,16,18-21,30H,9-10,12-15H2,1-4H3,(H,26,31)/t18?,19-,20+,21-/m0/s1
InChI Key HXLOHDZQBKCUCR-VTHDOGFWSA-N
References
1. Baker DE. (2005)
Rationale for using serotonergic agents to treat irritable bowel syndrome.
Am J Health Syst Pharm, 62 (7): 700-11; quiz 712-3. [PMID:15790796]
2. Gershon MD, Tack J. (2007)
The serotonin signaling system: from basic understanding to drug development for functional GI disorders.
Gastroenterology, 132 (1): 397-414. [PMID:17241888]
3. Hansen MB, Skadhauge E. (1997)
Signal transduction pathways for serotonin as an intestinal secretagogue.
Comp Biochem Physiol A Physiol, 118 (2): 283-90. [PMID:9366057]
4. Kadowaki M, Wade PR, Gershon MD. (1996)
Participation of 5-HT3, 5-HT4, and nicotinic receptors in the peristaltic reflex of guinea pig distal colon.
Am J Physiol, 271 (5 Pt 1): G849-57. [PMID:8944700]
5. Kim DY, Camilleri M. (2000)
Serotonin: a mediator of the brain-gut connection.
Am J Gastroenterol, 95 (10): 2698-709. [PMID:11051338]
6. Long DD, Armstrong SR, Beattie DT, Choi SK, Fatheree PR, Gendron RA, Genov D, Goldblum AA, Humphrey PP, Jiang L et al.. (2012)
Discovery, oral pharmacokinetics and in vivo efficacy of velusetrag, a highly selective 5-HT(4) receptor agonist that has achieved proof-of-concept in patients with chronic idiopathic constipation.
Bioorg Med Chem Lett, 22 (19): 6048-52. [PMID:22959244]
7. Manabe N, Wong BS, Camilleri M. (2010)
New-generation 5-HT4 receptor agonists: potential for treatment of gastrointestinal motility disorders.
Expert Opin Investig Drugs, 19 (6): 765-75. [PMID:20408739]
8. Mozaffari S, Didari T, Nikfar S, Abdollahi M. (2014)
Phase II drugs under clinical investigation for the treatment of chronic constipation.
Expert Opin Investig Drugs, 23 (11): 1485-97. [PMID:24960333]
9. Smith JA, Beattie DT, Marquess D, Shaw JP, Vickery RG, Humphrey PP. (2008)
The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity.
Naunyn Schmiedebergs Arch Pharmacol, 378 (1): 125-37. [PMID:18415081]