INF39 |
| Catalog No.GC19201 |
INF39 is an irreversible and noncytotoxic NLRP3 inhibitor.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 866028-26-4
Sample solution is provided at 25 µL, 10mM.
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INF39 is an irreversible and noncytotoxic NLRP3 inhibitor.
INF39 is able to significantly inhibit ATP- and nigericin-induced IL-1β release at 10 uM. INF39 reduces caspase-1 activation and pyroptosis in the macrophages. INF39 can block not only NLRP3 activation but also the NF-κB pathway. INF39 potentially reacts with Cys-SH residues in the active site of cysteine protease caspase-1, but does not directly target caspase-1 activity. INF39 is able to reduce the steady state (or basal) BRET signal of NLRP3 without affecting the viability of cells, meaning that it can interfere with the basal NLRP3 conformation. INF39 does not block the initial conformational changes suffered by NLRP3 upon sensing the decrease of intracellular K+; however, it affects a second step of NLRP3 conformational change that could be related with the ATPase activity of the receptor and be independent of the decrease of intracellular K+. INF39 reaches the intestinal epithelium without undergoing chemical modifications. After absorption into epithelial cells, it is likely to act locally at the mucosal epithelial level[1].
Oral administration of INF39 reduces systemic and colonic inflammation in rats treated with 2,4- dinitrobenzenesulfonic acid. Significant increments of body weight are observed in inflamed rats under treatment with INF39 (12.5, 25, and 50 mg/ kg). Treatment with DNBS results in a significant increment of spleen weight (+39.3%). Such an increase is significantly reduced by administration of INF39 (+2.2, +4.3 and +4.8% at 12.5, 25, 50 mg/kg, respectively). The inhibition of NLRP3 inflammasome complex with INF39 dose-dependently attenuates the decrease in colonic length (-19, -13 and -8% at 12.5, 25, 50 mg/kg, respectively). Rats treated with INF39 displays a significant reduction of macroscopic damage score (4.7 at 12.5 mg/kg, 3.1 at 25 mg/kg, and 2.8 at 50 mg/kg). Oral administration of INF39 reduces colonic myeloperoxidase, IL-1β, and TNF Levels in DNBS-treated rats[1].
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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Kinase experiment: |
INF39 (100 μM final concentration, 2% DMSO) is added to wells containing immobilized NALP3 protein and preincubated for 55 min at 37°C to mimic normal experimental time (15 min preincubation+40 min incubation with ATP); in the control wells a mixture of buffer and DMSO is added. After the preincubation time the wells areished three times with reaction buffer, and ATP (250 μM) is added for 40 min at 37°C. ADP formation is measured with ADP-Glo-Assay[1]. |
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Animal experiment: |
Rats:DNBS-untreated and DNBS treated animals are assigned to the following treatment groups: INF39 (12.5, 25, 50 mg/kg/day) or dexamethasone (DEX, 1 mg/kg/day). INF39 and dexamethasone are suspended in olive oil and 1% methylcellulose, respectively, and administered in a volume of 0.2 mL/rat. DNBS-untreated animals (control group) and DNBS-treated rats (colitis group) received drug vehicle to serve as controls. Body weight is monitored daily starting from the onset of drug treatments[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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| Cas No. | 866028-26-4 | SDF | |
| Canonical SMILES | O=C(OCC)C(CC1=CC=CC=C1Cl)=C | ||
| Formula | C12H13ClO2 | M.Wt | 224.68 |
| Solubility | DMSO : 1 mg/mL (4.45 mM) | Storage | Store at -20°C,unstable in solution, ready to use. |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)
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