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Purity: ≥98%
INF39 (INF-39; INF 39), an acrylate derivative, is a potent, irreversible and nontoxic inhibitor of NLRP3 with potential anti-inflammatory activity. It is able to block the release of IL-1β (interleukin-1β) from macrophages. Pharmacological inhibition of NLRP3 inflammasome activation by INF39 may offer a new approach in the treatment of inflammatory bowel disease. In vivo studies confirmed the ability of the selected lead to alleviate the effects of colitis induced by 2,4-dinitrobenzenesulfonic acid in rats after oral administration. Bioluminescence resonance energy transfer experiments proved that INF39 was able to directly interfere with NLRP3 activation in cells.
| ln Vitro |
At 10 μM, ATP and nigericin may both strongly suppress the release of IL-1β, which is triggered by INF39. INF39 inhibits the macrophages' pyroptosis and caspase-1 activation. INF39 has the ability to inhibit both the NF-κB pathway and NLRP3 activation. Although it does not specifically target caspase-1 activity, INF39 may interact with Cys-SH residues in the cysteine protease caspase-1's active site. It is possible for INF39 to disrupt the basal NLRP3 conformation by lowering the steady state (or basal) BRET signal of NLRP3 without impairing cell survival. INF39 affects a second step of NLRP3 conformational change that may be connected to the receptor's ATPase activity and independent of the decrease in intracellular K+. However, it does not prevent the first conformational changes that NLRP3 experiences upon sensing the decrease in intracellular K+. INF39 travels without changing chemically to reach the intestinal epithelium. It is probably going to operate locally at the mucosal epithelial level after being absorbed into epithelial cells[1].
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| ln Vivo |
Rats given 2,4-dinitrobenzenesulfonic acid treatment exhibit decreased colonic and systemic inflammation upon oral delivery of INF39. Adequate increases in body weight are noted in inflammatory rats receiving INF39 (12.5, 25, and 50 mg/kg). Spleen weight increases significantly (+39.3%) after receiving DNBS treatment. INF39 treatment considerably reduces such an increase (+2.2, +4.3, and +4.8% at 12.5, 25, and 50 mg/kg, respectively). The reduction in colonic length (−19, −13, and −8% at 12.5, 25, and 50 mg/kg, respectively) is dose-dependently attenuated by the inhibition of NLRP3 inflammasome complex with INF39. The macroscopic damage score in rats treated with INF39 significantly decreased (to 4.7 at 12.5 mg/kg, 3.1 at 25 mg/kg, and 2.8 at 50 mg/kg). In rats treated with DNBS, oral treatment of INF39 lowers levels of TNF, IL-1β, and colonic myeloperoxidase[1].
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| References |
[1]. Cocco M, et al. Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the Treatment of Inflammatory Bowel Disease.J Med Chem. 2017 May 11;60(9):3656-3671
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| Molecular Formula |
C12H13CLO2
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| Molecular Weight |
224.68
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| CAS # |
866028-26-4
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| SMILES |
ClC1=C(CC(C(OCC)=O)=C)C=CC=C1
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| 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)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.13 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 (11.13 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (11.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4508 mL | 22.2539 mL | 44.5077 mL | |
| 5 mM | 0.8902 mL | 4.4508 mL | 8.9015 mL | |
| 10 mM | 0.4451 mL | 2.2254 mL | 4.4508 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
J Med Chem.2017 May 11;60(9):3656-3671. Graphic abstract: Compound 11 is IFN39 |
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