VGX-1027

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Background

VGX-1027 is a potent immunomodulatory agent [1].
Immunotherapy refers to treatment of disease by suppressing, inducing or enhancing an immune response.
VGX-1027 is an isoxazoline compound with potent immunomodulatory properties [1]. In microarray analysis, VGX-1027 modulated the expression of genes that involved in immune activation and the antigen processing and presentation in response to lipopolysaccharide (LPS) stimulation [2]. In CD4+CD25− T cells, VGX-1027 inhibited cell proliferation induced by enterobacterial antigen [3].
In NOD mice with spontaneous or accelerated diabetes, VGX-1027 significantly reduced the incidence of insulitis and diabetes. In CBA/H mice, VGX-1027 significantly inhibited the development of hyperglycemia and destructive insulitis induced by multiple low doses of streptozotocin. Also, VGX-1027 inhibited the production of inducible nitric-oxide synthase-mediated nitric oxide, macrophage migration inhibitory factor, proinflammatory mediators tumor necrosis factor-α and IL-1β in pancreatic islets [1]. In NZB/NZW F1 mice with systemic lupus erythematosus (SLE), VGX-1027 ameliorated the disease and increased survival [2]. In mice with acute inflammatory colitis, VGX-1027 inhibited the development of colitis. Also, VGX-1027 reduced the production of proinflammatory cytokines TNF-α, IL-12p70, interleukin (IL)-1β, interferon (IFN)-γ and nuclear factor NF-κB (p65) [3].

[1]. Stosic-Grujicic S, Cvetkovic I, Mangano K, et al. 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, 2007, 320(3): 1038-1049.
[2]. Fagone P, Muthumani K, Mangano K, et al. VGX-1027 modulates genes involved in lipopolysaccharide-induced Toll-like receptor 4 activation and in a murine model of systemic lupus erythematosus. Immunology, 2014, 142(4): 594-602.
[3]. Mangano K, Sardesai N, D'Alcamo M, et al. 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, 2008, 586(1-3): 313-321.