| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
Tumor Necrosis Factor-alpha (TNF-alpha). TNF-alpha is a key pro-inflammatory cytokine involved in systemic inflammation and is a major therapeutic target for autoimmune diseases like rheumatoid arthritis and psoriasis. Benpyrine is a direct inhibitor that binds to soluble TNF-alpha, preventing it from interacting with its receptor TNFR1, thereby blocking downstream inflammatory signaling.
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| ln Vitro |
Benpyrine binds to TNF-alpha with a KD of 82.1 microM. It blocks the TNF-alpha/TNFR1 interaction with an IC50 of 0.109 microM. This binding is highly specific, preventing the cytokine from triggering its pro-inflammatory signaling cascade. (R)-Benpyrine, as the inactive isomer, is used as a negative control to validate the specific TNF-alpha-inhibiting activity of the parent compound in cell-based assays.
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| ln Vivo |
In vivo activity data for Benpyrine is available. As an orally active TNF-alpha inhibitor, it is used in animal models of inflammatory diseases. Benpyrine effectively blocks TNF-alpha-mediated inflammation, making it a promising candidate for treating conditions like rheumatoid arthritis, inflammatory bowel disease, and psoriasis. (R)-Benpyrine is used as a control in these experiments to verify that the observed therapeutic effects are due to specific TNF-alpha antagonism.
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| Enzyme Assay |
A non-cell binding assay can be used to measure the direct interaction between a compound and TNF-alpha. Surface plasmon resonance (SPR) or a similar technique is used to determine the binding affinity (KD). Recombinant human TNF-alpha is immobilized on a sensor chip, and varying concentrations of the test compound are flowed over the surface. The resulting sensorgrams are analyzed to calculate the association and dissociation rates, which are used to determine the KD value.
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| Cell Assay |
A cell-based assay to confirm TNF-alpha antagonism involves using a reporter cell line. A cell line engineered to express TNFR1 and a luciferase reporter gene under the control of a NF-kappaB responsive element is used. The cells are treated with TNF-alpha to activate the NF-kappaB pathway, which leads to luciferase expression. The test compound is added to the culture, and a reduction in luminescence indicates successful blockade of the TNF-alpha/TNFR1 interaction.
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| Animal Protocol |
In vivo efficacy of Benpyrine is typically evaluated in a mouse model of collagen-induced arthritis (CIA), a well-established model for rheumatoid arthritis. Mice are immunized with collagen to induce joint inflammation. Benpyrine is administered orally once or twice daily for several weeks. Arthritis scores are monitored by clinical assessment of paw swelling, and joint damage is evaluated histologically. (R)-Benpyrine is used as a negative control.
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| ADME/Pharmacokinetics |
Benpyrine is an orally active small molecule. In vitro, it is soluble in DMSO at a concentration of 6.67 mg/mL (21.63 mM). For in vivo studies, it can be formulated in a vehicle such as PEG300 or a combination of DMSO/PEG300/Tween-80/saline. Detailed PK parameters such as half-life, Cmax, and bioavailability are not provided in the datasheet but are typical for an orally bioavailable small molecule.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for (R)-Benpyrine. The parent compound, Benpyrine, is a highly specific TNF-alpha inhibitor. TNF-alpha inhibitors as a class are known to have potential side effects including increased risk of infections and possible infusion reactions. However, no overt toxicity has been reported in the available literature for Benpyrine at its effective doses. Comprehensive safety data is not available as the compound is for research use.
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| References |
[1]. Weiguang Sun, et al. Discovery of an Orally Active Small Molecule TNF-α Inhibitor. J Med Chem. 2020 Jul 15.
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| Additional Infomation |
Benpyrine is a research-grade chemical used to study TNF-alpha-mediated inflammatory diseases. The discovery of an orally active small molecule inhibitor of TNF-alpha represents a significant advance, as current FDA-approved TNF-alpha inhibitors are biologics that require injection. This product is for research use only and is not FDA-approved for human use. A key reference is Sun W, et al. J Med Chem. 2020 Jul 15.
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| Molecular Formula |
C16H16N6O
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| Molecular Weight |
308.34
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| Related CAS # |
Benpyrine;2550398-89-3;(Rac)-Benpyrine;1333714-43-4
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| Appearance |
Off-white to light yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2432 mL | 16.2159 mL | 32.4317 mL | |
| 5 mM | 0.6486 mL | 3.2432 mL | 6.4863 mL | |
| 10 mM | 0.3243 mL | 1.6216 mL | 3.2432 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.
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