GW274150   Click here for help

GtoPdb Ligand ID: 9849

Synonyms: [2-[(1-iminoethyl) amino]ethyl]-L-homocysteine | GW-274150
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: GW274150 is a selective inducible nitric oxide synthase (iNOS) inhibitor that is active in vitro and in vivo [1].
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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

GW274150 is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 5
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 127
Molecular weight 219.1
XLogP -2.41
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC(=NCCSCCC(C(=O)O)N)N
Isomeric SMILES CC(=NCCSCC[C@@H](C(=O)O)N)N
InChI InChI=1S/C8H17N3O2S/c1-6(9)11-3-5-14-4-2-7(10)8(12)13/h7H,2-5,10H2,1H3,(H2,9,11)(H,12,13)/t7-/m0/s1
InChI Key MOLOJNHYNHBPCW-ZETCQYMHSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Alderton WK, Angell AD, Craig C, Dawson J, Garvey E, Moncada S, Monkhouse J, Rees D, Russell LJ, Russell RJ et al.. (2005)
GW274150 and GW273629 are potent and highly selective inhibitors of inducible nitric oxide synthase in vitro and in vivo.
Br J Pharmacol, 145 (3): 301-12. [PMID:15778742]
2. Alderton WK, Cooper CE, Knowles RG. (2001)
Nitric oxide synthases: structure, function and inhibition.
Biochem J, 357 (Pt 3): 593-615. [PMID:11463332]
3. Boughton-Smith NK, Tinker AC. (1998)
Inhibitors of nitric oxide synthase in inflammatory arthritis.
IDrugs, 1 (3): 321-33. [PMID:18465556]
4. Connolly S, Aberg A, Arvai A, Beaton HG, Cheshire DR, Cook AR, Cooper S, Cox D, Hamley P, Mallinder P et al.. (2004)
2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors. Differential binding modes dependent on nitrogen substitution.
J Med Chem, 47 (12): 3320-3. [PMID:15163211]
5. De Alba J, Clayton NM, Collins SD, Colthup P, Chessell I, Knowles RG. (2006)
GW274150, a novel and highly selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), shows analgesic effects in rat models of inflammatory and neuropathic pain.
Pain, 120 (1-2): 170-81. [PMID:16360270]
6. Hesslinger C, Strub A, Boer R, Ulrich WR, Lehner MD, Braun C. (2009)
Inhibition of inducible nitric oxide synthase in respiratory diseases.
Biochem Soc Trans, 37 (Pt 4): 886-91. [PMID:19614613]
7. Hoffmann J, Goadsby PJ. (2012)
New Agents for Acute Treatment of Migraine: CGRP Receptor Antagonists, iNOS Inhibitors.
Curr Treat Options Neurol, 14 (1): 50-9. [PMID:22090312]
8. Høivik HO, Laurijssens BE, Harnisch LO, Twomey CK, Dixon RM, Kirkham AJ, Williams PM, Wentz AL, Lunnon MW. (2010)
Lack of efficacy of the selective iNOS inhibitor GW274150 in prophylaxis of migraine headache.
Cephalalgia, 30 (12): 1458-67. [PMID:20974604]
9. Seymour M, Pétavy F, Chiesa F, Perry H, Lukey PT, Binks M, Donatien PD, Freidin AJ, Eckersley RJ, McClinton C et al.. (2012)
Ultrasonographic measures of synovitis in an early phase clinical trial: a double-blind, randomised, placebo and comparator controlled phase IIa trial of GW274150 (a selective inducible nitric oxide synthase inhibitor) in rheumatoid arthritis.
Clin Exp Rheumatol, 30 (2): 254-61. [PMID:22409880]