VGX-1027 is a small molecule, isoxazoline compound that can decrease the production of tumor necrosis factor-α production from macrophages in response to the activation of Toll-like receptors. It has been shown to significantly downregulate the expression of MHC class II molecules, including HLA-DPB1, HLA-DOB, HLA-DRA, IFNG, HIST2H2AB, HIST1H2BM, and FCGR3A at a concentration of 10μM. VGX-1027 treatment also significantly suppressed lipopolysaccharide-induced upregulation of cytokine (e.g. interleukin-22) and chemokines (e.g. CCL8). In the NZB/NZW F1 mouse model of systemic lupus erythematosus, daily intraperitoneal administration with 5mg VGX-1027 for 20 weeks reduced proteinuria and prolonged survival of mice compared with the vehicle-treated control group. Treatment of NZB/NZW F1 mice with VGX-1027 (20mg/day, intraperitoneal injection) for 20 weeks reduced anti-dsDNA autoantibodies in the serum, downregulated cytokine production, and suppressed the development of nephritis compared with the controls[3].
VGX-1027 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Peripheral blood mononuclear cells
10 µM
48 hours
To study the immunomodulatory effects of VGX-1027 on LPS-induced Toll-like receptor 4 activation, results showed that VGX-1027 significantly altered the gene expression profile, particularly downregulating genes involved in antigen processing and presentation.
Immunology. 2014 Aug;142(4):594-602
HepG2 cells
1000, 500, 250 nM
5 hours
To evaluate the protective effects of GIT-27NO and VGX-1027 against H2O2-induced oxidative stress. GIT-27NO significantly counteracted the toxic effects of H2O2, while VGX-1027 showed only mild protection at the highest concentration.
Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419862736
Human podocytes
10 μg/ml
72 hours
To investigate the effect of GIT27 on podocyte apoptosis induced by sera with high LPS activity, results showed that GIT27 pretreatment prevented downregulation of PDK1 expression and reduced apoptosis.
Cell Death Dis. 2015 May 7;6(5):e1752
VGX-1027 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB-C mice
LPS-induced podocyte injury and proteinuria model
Intraperitoneal injection
20 mg/kg
24 hours before and 2 hours after LPS challenge
To evaluate the protective effect of GIT27 on LPS-induced podocyte injury, results showed that GIT27 treatment prevented the decrease in PDK1 expression and podocyte apoptosis.
Cell Death Dis. 2015 May 7;6(5):e1752
NZB/NZW F1 mice
Systemic lupus erythematosus model
Intraperitoneal injection
20 mg/kg
Daily for 20 weeks
To evaluate the effects of VGX-1027 on the systemic lupus erythematosus model, results showed that VGX-1027 significantly improved survival, reduced proteinuria and kidney pathology, and decreased anti-dsDNA antibody and cytokine production.
Immunology. 2014 Aug;142(4):594-602
Lewis rats
Endotoxin-induced uveitis (EIU) model
Intraperitoneal injection
25 mg/kg
Single dose, at 30 min, 6 h or 12 h after LPS injection
VGX-1027 significantly alleviated clinical, histological and laboratory signs of EIU when administered within 6 h after LPS challenge
Br J Pharmacol. 2008 Nov;155(5):722-30
Mice
Controlled cortical impact (TBI) model
Tail vein injection
50 mg/kg
Single dose, 4 hours post-injury
To evaluate the effect of VGX-1027 on cerebral edema after TBI. A 4h post-treatment significantly attenuated edema, while pre-treatment or 1h post-treatment was ineffective.
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