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VGX-1027 (also known as VGX1027; GIT-27) is an orally bioactive, isoxazoline compound with potent immunomodulatory properties by inhibiting the toll-like receptor 4 (TLR4) signaling pathway. By reducing the cytotoxic effects of the cytokines, VGX-1027 significantly reduces IIL-1β/IFN-γ-induced TNF-α and nitrite accumulation and increases cell survival. When lipopolysaccharide (LPS) stimulation was used, the microarray analysis showed that VGX-1027 altered the expression of genes involved in immune activation, antigen processing, and presentation.
Physicochemical Properties
| Molecular Formula | C11H11NO3 | |
| Molecular Weight | 205.21 | |
| Exact Mass | 205.073 | |
| Elemental Analysis | C, 64.38; H, 5.40; N, 6.83; O, 23.39 | |
| CAS # | 6501-72-0 | |
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| PubChem CID | 10798271 | |
| Appearance | White to off-white solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 381.4±34.0 °C at 760 mmHg | |
| Melting Point | 159 °C | |
| Flash Point | 184.5±25.7 °C | |
| Vapour Pressure | 0.0±0.9 mmHg at 25°C | |
| Index of Refraction | 1.601 | |
| LogP | 1.16 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 3 | |
| Heavy Atom Count | 15 | |
| Complexity | 269 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | O1C([H])(C([H])([H])C(=O)O[H])C([H])([H])C(C2C([H])=C([H])C([H])=C([H])C=2[H])=N1 |
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| InChi Key | MUFJHYRCIHHATF-UHFFFAOYSA-N | |
| InChi Code | 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) | |
| Chemical Name | 2-(3-phenyl-4,5-dihydro-1,2-oxazol-5-yl)acetic acid | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | IL-1β; IL-10 | ||
| ln Vitro | VGX-1027 (37.5, 75, 150, 300 μM; for 24 h) does not affect the viability of tumor cells，including the three malignant rodent cell lines (mouse fibrosarcoma L929, rat astrocytoma C6, and mouse melanoma B16) and the four human cell lines (adenocarcinoma HeLa, breast carcinoma BT20, colon carcinoma LS174, and glioblastoma U251)[2]. | ||
| ln Vivo | VGX-1027 effectively prevents the onset of destructive insulitis and hyperglycemia (10, 20 mg/kg of i.p. for 12 day or 100 mg/kg of p.o. for 11 day) [1]. In eight-week-old male Lewis rats (180-220 g), VGX-1027 (25 mg/kg; ip; single dose) blocks LPS's ability to cause uveitis[3]. | ||
| Cell Assay | 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. In CD4+CD25− T cells, VGX-1027 inhibited cell proliferation induced by enterobacterial antigen. | ||
| Animal Protocol |
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| References |
[1]. 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 Mar;320(3):1038-49. [2]. Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo. Mol Cancer Ther. 2008 Mar;7(3):510-20. [3]. Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats. Br J Pharmacol. 2008 Nov;155(5):722-30. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (12.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (12.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (12.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 2% DMSO +30%PEG 300 +5% Tween 80 +ddH2O: 10mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.8731 mL | 24.3653 mL | 48.7306 mL | |
| 5 mM | 0.9746 mL | 4.8731 mL | 9.7461 mL | |
| 10 mM | 0.4873 mL | 2.4365 mL | 4.8731 mL |