ZENUZOLAC

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H11NO3
Molecular Weight	205.2099
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC1CC(=NO1)C2=CC=CC=C2

InChI

InChIKey=MUFJHYRCIHHATF-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C11H11NO3
Molecular Weight	205.2099
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://adisinsight.springer.com/drugs/800025945
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17148780 | https://www.ncbi.nlm.nih.gov/pubmed/17449326

(S,R)-3-Phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027, GIT-027) is an isoxazole compound that exhibits various immunomodulatory properties. This compound reduced the secretion of IL-1beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappaB and p38 MAP kinase pathways along with up-regulation of ERK pathways. The animals receiving VGX-1027 exhibited reduced production of the proinflammatory mediators tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, and inducible nitric-oxide synthase-mediated nitric oxide generation in both pancreatic islets and peripheral compartments. Inovio Pharmaceuticals is developing VGX-1027 for the treatment of inflammatory conditions such as rheumatoid arthritis, type 1 diabetes mellitus, uveitis and ulcerative colitis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
regulation of cytokine biosynthetic process 1 Target ID: GO:0042035 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17148780 \| https://www.ncbi.nlm.nih.gov/pubmed/17449326	Modulator 828
Toll signaling pathway 1 Target ID: GO:0008063 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25950482 \| https://www.ncbi.nlm.nih.gov/pubmed/24166800 \| https://www.ncbi.nlm.nih.gov/pubmed/23568555	Inhibitor 8297
apoptotic process 48 Target ID: GO:0006915 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25950482	Inhibitor 8297
p38MAPK cascade 8 Target ID: GO:0038066 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17449326	Inhibitor 8297
NF-kappa B signaling pathway 84 Target ID: map04064 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17449326 \| https://www.ncbi.nlm.nih.gov/pubmed/18374912	Inhibitor 8297
inflammatory response 47 Target ID: GO:0006954 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17148780 \| https://www.ncbi.nlm.nih.gov/pubmed/17449326 \| https://www.ncbi.nlm.nih.gov/pubmed/17449326	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 1 diabetes mellitus 17 Sources: http://adisinsight.springer.com/drugs/800025945	Primary		Phase II 1132	Unknown Approved Use Unknown
Rheumatoid arthritis 316 Sources: http://adisinsight.springer.com/drugs/800025945	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
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.	2007 Jun	17449326
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.	2007 Mar	17148780
In vitro inhibition of enterobacteria-reactive CD4+CD25- T cells and suppression of immunoinflammatory colitis in mice by the novel immunomodulatory agent VGX-1027.	2008 May 31	18374912
Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats.	2008 Nov	18776919
VGX-1027 modulates genes involved in lipopolysaccharide-induced Toll-like receptor 4 activation and in a murine model of systemic lupus erythematosus.	2014 Aug	24527796

Patents

Sample Use Guides

In Vivo Use Guide

The safety, tolerability, and pharmacokinetics of single (1-800 mg) and multiple (40-400 mg) oral doses were evaluated in 2 clinical studies (NCT00627120, NCT00760396). The doses were well tolerated up to 800 mg in a single dose and 200 mg twice daily in multiple doses.

Route of Administration: Other

In Vitro Use Guide

Treatment with VGX-1027 (GIT-027) 25 μM eliminated the stimulatory effect of NMDA-treated neuronal-CM in (A) mouse C8-B4 microglial cells and (B) in primary human microglia.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:37:14 GMT 2023` Edited by `admin` on `Sat Dec 16 11:37:14 GMT 2023`
Record UNII	AKT814N13R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZENUZOLAC

Official Name

English

GLS 1027 [WHO-DD]

Common Name

English

GIT-027

Code

English

(S,R)-3-PHENYL-4,5-DIHYDRO-5-ISOXASOLE ACETIC ACID

Systematic Name

English

GLS-1027

Code

English

VGX-1027

Code

English

VGX1027

Code

English

2-ISOXAZOLINE-5-ACETIC ACID, 3-PHENYL-

Systematic Name

English

4,5-DIHYDRO-3-PHENYL-5-ISOXAZOLEACETIC ACID

Systematic Name

English

GLS1027

Code

English

5-ISOXAZOLEACETIC ACID, 4,5-DIHYDRO-3-PHENYL-

Systematic Name

English

zenuzolac [INN]

Common Name

English

GIT-27

Code

English

Code System Code Type Description

NCI_THESAURUS

C184883