zenuzolac   Click here for help

GtoPdb Ligand ID: 11682

Synonyms: (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid | GIT-027 | GIT-27 | GIT27 | GLS-1027 | GLS1027 | rac-[(5R)-3-phenyl-4,5-dihydro-1,2-oxazol-5-yl]acetic acid | VGX-1027 | VGX1027
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: We obtained the chemical structure for zenuzolac from WHO Proposed list 125 of July 2021, in which it is described as an anti-inflammatory. The INN represents the racemic (rac) mixture of (R) and (S) enantiomers. We show the molecule without specified stereochemistry to represent the mixture. We have mapped this to PubChem CID 10798271. Synonyms from the PubChem entry associate the structure with research code VGX-1027 (VGX Pharmaceuticals). VGX-1027 is an immunomodulatory compound that downregulates proinflammatory cytokine production and NF-κB and MAP kinase activation [1,4-5].

COVID-19: Zenuzolac (re-named as GLS-1027) is being evaluated to determine its potential to reduce SARS-CoV-2-induced pulmonary inflammation (pneumonitis).
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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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 2
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 58.89
Molecular weight 205.07
XLogP 1.93
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(=O)CC1ON=C(C1)c1ccccc1
Isomeric SMILES C1C(ON=C1c1ccccc1)CC(=O)O
InChI InChI=1S/C11H11NO3/c13-11(14)7-9-6-10(12-15-9)8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H,13,14)
InChI Key MUFJHYRCIHHATF-UHFFFAOYSA-N
References
1. Fagone P, Muthumani K, Mangano K, Magro G, Meroni PL, Kim JJ, Sardesai NY, Weiner DB, Nicoletti F. (2014)
VGX-1027 modulates genes involved in lipopolysaccharide-induced Toll-like receptor 4 activation and in a murine model of systemic lupus erythematosus.
Immunology, 142 (4): 594-602. [PMID:24527796]
2. Mangano K, Sardesai N, D'Alcamo M, Libra M, Malaguarnera L, Donia M, Bendtzen K, Meroni P, Nicoletti F. (2008)
In vitro inhibition of enterobacteria-reactive CD4+CD25- T cells and suppression of immunoinflammatory colitis in mice by the novel immunomodulatory agent VGX-1027.
Eur J Pharmacol, 586 (1-3): 313-21. [PMID:18374912]
3. Mangano K, Sardesai NY, Quattrocchi C, Mazzon E, Cuzzocrea S, Bendtzen K, Meroni PL, Kim JJ, Nicoletti F. (2008)
Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats.
Br J Pharmacol, 155 (5): 722-30. [PMID:18776919]
4. McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN. (2008)
Autism-like behavioral phenotypes in BTBR T+tf/J mice.
Genes Brain Behav, 7 (2): 152-63. [PMID:17559418]
5. Silverman JL, Tolu SS, Barkan CL, Crawley JN. (2010)
Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP.
Neuropsychopharmacology, 35 (4): 976-89. [PMID:20032969]
6. Stojanovic I, Cuzzocrea S, Mangano K, Mazzon E, Miljkovic D, Wang M, Donia M, Al Abed Y, Kim J, Nicoletti F et al.. (2007)
In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models.
Clin Immunol, 123 (3): 311-23. [PMID:17449326]
7. Stosic-Grujicic S, Cvetkovic I, Mangano K, Fresta M, Maksimovic-Ivanic D, Harhaji L, Popadic D, Momcilovic M, Miljkovic D, Kim J et al.. (2007)
A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid, prevents spontaneous and accelerated forms of autoimmune diabetes in NOD mice and inhibits the immunoinflammatory diabetes induced by multiple low doses of streptozotocin in CBA/H mice.
J Pharmacol Exp Ther, 320 (3): 1038-49. [PMID:17148780]