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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
BMS-561392 formate targets TNF alpha-converting enzyme (TACE), also known as ADAM17 (a disintegrin and metalloproteinase domain-containing protein 17). TACE is a zinc-dependent metalloproteinase that is responsible for the proteolytic cleavage of membrane-bound pro-TNF-α, releasing soluble TNF-α into the circulation and tissues. TNF-α is a pleiotropic pro-inflammatory cytokine that plays a central role in the pathogenesis of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. By inhibiting TACE, BMS-561392 formate reduces the production of soluble TNF-α, thereby modulating inflammatory responses. The compound also regulates TNF-α secretion through modulation of p44 MAPK and NFκB signaling pathways, indicating that it may have additional effects beyond direct enzyme inhibition. BMS-561392 formate is a selective TACE inhibitor, making it a useful tool for studying the specific role of TACE in TNF-α biology and inflammation.
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| ln Vitro |
In vitro, BMS-561392 formate acts as a potent and selective inhibitor of TACE/ADAM17 activity. The compound inhibits TNF-α secretion by blocking the proteolytic cleavage of pro-TNF-α. It regulates TNF-α secretion through modulation of p44 MAPK and NFκB signaling pathways, suggesting that its effects may extend beyond direct enzyme inhibition to include modulation of downstream signaling cascades. BMS-561392 formate also affects oligodendrocyte function, indicating potential effects on cells of the central nervous system. The compound's selectivity for TACE over other metalloproteinases makes it a valuable research tool for dissecting the specific role of TACE in various biological processes. However, specific quantitative data such as IC50 values for TACE inhibition have not been extensively reported in the available literature. The compound is used primarily in research on inflammatory diseases and neuroinflammatory conditions.
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| ln Vivo |
In vivo activity of BMS-561392 formate has been studied in the context of inflammatory diseases, particularly inflammatory bowel disease (IBD). By inhibiting TACE and reducing TNF-α production, the compound would be expected to attenuate inflammation in animal models of IBD and other inflammatory conditions. However, specific details regarding the animal models used, dosing regimens, and quantitative outcomes have not been extensively reported in the available literature. The compound's effects on oligodendrocytes suggest potential applications in neuroinflammatory conditions such as multiple sclerosis, but in vivo data in these models are limited. Further in vivo studies would be required to fully characterize the compound's efficacy, safety, and pharmacokinetic properties in various disease models. The compound is intended for research use only.
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| Enzyme Assay |
In vitro enzyme assay protocols for BMS-561392 formate would typically involve measuring the inhibition of TACE/ADAM17 enzymatic activity using fluorogenic or chromogenic peptide substrates. A standard protocol would involve incubating recombinant human TACE or TACE-containing membrane preparations with varying concentrations of BMS-561392 formate (typically 0.1 nM to 10 μM) and a fluorogenic substrate such as a peptide containing the TNF-α cleavage site with a fluorophore-quencher pair (e.g., Mca-PLAQAV-Dpa-RSSSR-NH2) in assay buffer (e.g., Tris-HCl, pH 7.4, with appropriate salts) at 37°C for a defined period (e.g., 30-120 minutes). The reaction is terminated, and fluorescence is measured using a fluorescence plate reader. The rate of substrate cleavage is calculated, and IC50 values are determined from concentration-response curves. Selectivity assays using other ADAM family members or MMPs can be performed to assess the compound's specificity.
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| Cell Assay |
In vitro cell-based assay protocols for BMS-561392 formate typically involve assessing its effects on TNF-α secretion from cultured cells. A standard protocol would involve seeding cells that produce TNF-α (e.g., LPS-stimulated monocytes or macrophages, or cell lines such as THP-1) in multi-well plates. Cells are treated with varying concentrations of BMS-561392 formate (typically 0.1 nM to 10 μM) for a defined period (e.g., 1-4 hours), followed by stimulation with LPS or other inflammatory stimuli to induce TNF-α production. Culture supernatants are collected, and TNF-α levels are measured by ELISA. The compound's ability to inhibit TNF-α secretion is calculated as a percentage of the stimulated control. Effects on cell viability should be assessed using MTT or similar assays to ensure that observed effects are not due to cytotoxicity. Signaling pathway modulation (p44 MAPK, NFκB) can be assessed by Western blot analysis of phosphorylated proteins or by reporter gene assays.
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| Animal Protocol |
In vivo animal experimental protocols for BMS-561392 formate would typically involve administering the compound to animal models of inflammatory diseases. A standard protocol for studying its effects in inflammatory bowel disease might involve using mouse models such as dextran sulfate sodium (DSS)-induced colitis or TNBS-induced colitis. BMS-561392 formate would be administered orally or intraperitoneally at doses determined from preliminary studies (e.g., 1-30 mg/kg). Treatment would typically be initiated before or at the onset of disease and continued for the duration of the study (e.g., 7-14 days). Endpoints would include disease activity index (weight loss, stool consistency, rectal bleeding), colon length, histological assessment of inflammation, and measurement of TNF-α levels in colon tissue or serum. For studies of neuroinflammation, the compound could be administered in models of experimental autoimmune encephalomyelitis (EAE) or other relevant models. However, specific published protocols are limited.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of BMS-561392 formate have not been extensively characterized in published studies. As a small molecule inhibitor, the compound would be expected to have reasonable oral bioavailability and tissue distribution, but specific PK parameters such as half-life, Cmax, AUC, bioavailability, volume of distribution, and clearance have not been reported. The formate salt form may enhance solubility compared to the free base. The compound's metabolism, protein binding, and routes of elimination remain uncharacterized. Further pharmacokinetic studies would be required to understand its absorption, distribution, metabolism, and excretion profile. The compound is intended for research use only.
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| Toxicity/Toxicokinetics |
Toxicological data for BMS-561392 formate are limited, as the compound is intended for research use only and has not undergone systematic toxicity testing. No acute toxicity (LD50), subchronic toxicity, genotoxicity, or reproductive toxicity studies have been reported specifically for this compound. As a TACE inhibitor that reduces TNF-α production, potential on-target toxicities could include increased susceptibility to infections and impaired wound healing, which are known class effects of TNF-α inhibitors. However, these have not been evaluated specifically for BMS-561392 formate. The compound is not intended for human use. Researchers should follow standard safety precautions when handling the compound, including working in a fume hood, wearing appropriate personal protective equipment, and avoiding inhalation, ingestion, or skin contact.
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| References |
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| Additional Infomation |
BMS-561392 formate is a research-grade compound that functions as a potent and selective inhibitor of TNF alpha-converting enzyme (TACE/ADAM17). It modulates TNF-α secretion through inhibition of TACE and regulation of p44 MAPK and NFκB signaling pathways. The compound is used in research on inflammatory diseases, particularly inflammatory bowel disease, and also affects oligodendrocyte function. BMS-561392 formate has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves inhibition of TACE, preventing the cleavage of pro-TNF-α to soluble TNF-α, thereby reducing TNF-α-mediated inflammation. The compound is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
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| CAS # |
2922280-85-9
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| Appearance |
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) |
Typically soluble in DMSO (e.g. 10 mM)
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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.) |
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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