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| Targets |
The primary target of E-6087 is the enzyme cyclooxygenase-2 (COX-2). COX-2 is a key enzyme in the prostaglandin synthesis pathway. It is induced by pro-inflammatory cytokines, growth factors, and tumor promoters at sites of inflammation. The prostaglandins produced by COX-2 mediate the cardinal signs of inflammation: pain, swelling, redness, and fever. By selectively inhibiting COX-2, E-6087 reduces the production of these pro-inflammatory prostaglandins, thereby alleviating inflammation and pain. Its selectivity for COX-2 over COX-1 is its defining feature. This selectivity is designed to provide therapeutic efficacy while minimizing the gastrointestinal and renal toxicities that result from COX-1 inhibition.
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| ln Vitro |
E-6087 is a potent and selective inhibitor of COX-2. It does not inhibit COX-1. This selectivity is crucial for its potential as a safer NSAID. Its in vitro activity is typically measured using enzyme assays that compare its ability to inhibit COX-2 and COX-1. In these assays, the compound's IC₅₀ for COX-2 is significantly lower than its IC₅₀ for COX-1, indicating high selectivity. It has also been shown to significantly enhance the response to radiation in cancer models, reducing mean tumor volume to 32% of tumors treated with radiation alone. This suggests it may have additional applications beyond pain and inflammation.
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| ln Vivo |
One of enflicoxib's (E-6087) metabolites, E-6132, also suppresses COX-2. Rats were given a single oral dose of 5 mg/kg E-6087, and the peak plasma concentration of enflecoxib was greater than that of E-6132, suggesting that enflecoxib was primarily responsible for the observed activity [1]. After single oral and intravenous dosages in rats and dogs, enflacoxib (E-6087) exhibits a long elimination half-life (20–35 hours), low plasma clearance (0.10-0.22 L/h/kg), and a reasonably wide volume of distribution (2–6 L/kg). The pharmacokinetics of E-6132, a metabolite with pharmacological activity, and enflacoxib differ. Although E-6132 contributes to this action in later stages, the higher percentage of enflacoxib in the early stages shows that enflacoxib is the major component responsible for activity in vivo [2].
E-6087 has been studied in vivo for its anti-inflammatory and analgesic effects. It is being investigated for the treatment of osteoarthritis and pain, indicating that it has shown efficacy in animal models of these conditions. Additionally, its ability to enhance the response to radiation has been demonstrated in vivo, suggesting it could have a role in cancer therapy. These in vivo studies are crucial for validating its therapeutic potential. |
| Enzyme Assay |
The in vitro enzyme assay for E-6087 measures its ability to inhibit COX-1 and COX-2 activity. In these assays, purified COX-1 or COX-2 enzymes are incubated with arachidonic acid (the substrate) and a co-factor. The production of prostaglandins (e.g., PGE2) is measured. The assay is performed in the presence of varying concentrations of E-6087. A control without the inhibitor defines 100% enzyme activity. By comparing the IC₅₀ values for COX-1 and COX-2, the selectivity of the compound can be determined. This is a standard biochemical assay for characterizing COX inhibitors.
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| Cell Assay |
In vitro cell-based assays for E-6087 evaluate its ability to inhibit prostaglandin production in cells. Cells that express COX-2, such as macrophages or synoviocytes, are stimulated with LPS or IL-1β to induce COX-2 expression and prostaglandin production. The cells are then treated with E-6087, and the levels of prostaglandins (e.g., PGE2) in the culture medium are measured by ELISA. The reduction in prostaglandin levels in the presence of the compound is a measure of its cellular activity.
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| Animal Protocol |
Animal/Disease Models: Male and female Wistar rats (250 g) [1]
Doses: 5 mg/kg Route of Administration: gavage (10 mL/kg); single oral dose Experimental Results: plasma of E-6087 at peak Concentration higher than E-6132. In vivo animal studies for E-6087 are conducted to evaluate its anti-inflammatory and analgesic effects. Standard models include the carrageenan-induced paw edema model (for anti-inflammatory activity) and the acetic acid-induced writhing test or the formalin test (for analgesic activity). In these models, the compound is administered orally, and its effect on inflammation or pain-related behaviors is assessed. For its radiosensitizing effect, mouse xenograft models of cancer are used, where tumors are treated with radiation and E-6087, and tumor growth is monitored. |
| ADME/Pharmacokinetics |
E-6087 is a small molecule with a molecular weight of 405.34. Detailed pharmacokinetic data, such as its oral bioavailability and half-life, has been published in the literature, as indicated by a reference on the enantioselective HPLC determination of E-6087 in human plasma. This suggests that the compound has been studied in humans, likely in Phase I clinical trials.
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| Toxicity/Toxicokinetics |
Specific toxicity data for E-6087 is not detailed in the provided search results. As a selective COX-2 inhibitor, its safety profile is expected to be better than non-selective NSAIDs in terms of gastrointestinal toxicity, but it may still carry cardiovascular risks, as seen with other COX-2 inhibitors. It is classified as a research compound and is not intended for human use.
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| References |
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| Additional Infomation |
Drug Indication
For the treatment of pain and inflammation caused by osteoarthritis (or degenerative joint disease) in dogs. E-6087 (Enflicoxib) is a selective COX-2 inhibitor that has been investigated for the treatment of osteoarthritis and pain. It has also shown potential as a radiosensitizer in cancer therapy. The compound has been studied in humans, as indicated by the availability of a human plasma assay. However, it does not appear to have received FDA approval. |
| Molecular Formula |
C16H12F5N3O2S
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| Molecular Weight |
405.343
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| Exact Mass |
405.057
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| CAS # |
251442-94-1
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| PubChem CID |
9953093
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| Appearance |
White to off-white solid powder
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| LogP |
4.763
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
671
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZZMJXWXXMAAPLI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H12F5N3O2S/c17-9-1-6-12(13(18)7-9)14-8-15(16(19,20)21)23-24(14)10-2-4-11(5-3-10)27(22,25)26/h1-7,14H,8H2,(H2,22,25,26)
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| Chemical Name |
4-[3-(2,4-difluorophenyl)-5-(trifluoromethyl)-3,4-dihydropyrazol-2-yl]benzenesulfonamide
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| Synonyms |
E6087; E 6087; E-6087
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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) |
DMSO : ~100 mg/mL (~246.71 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4671 mL | 12.3353 mL | 24.6706 mL | |
| 5 mM | 0.4934 mL | 2.4671 mL | 4.9341 mL | |
| 10 mM | 0.2467 mL | 1.2335 mL | 2.4671 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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