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].
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