| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| Targets |
sEH inhibitor-7 targets soluble epoxide hydrolase (sEH), a bifunctional enzyme with epoxide hydrolase and lipid phosphate phosphatase activities. sEH is widely expressed in tissues including liver, kidney, vascular endothelium, and brain. The epoxide hydrolase activity of sEH converts anti-inflammatory epoxy-fatty acids (including EETs, epoxydocosapentaenoic acids, and epoxy-eicosatetraenoic acids) to less active diols, thereby terminating their biological activities. By inhibiting this enzyme, sEH inhibitor-7 preserves the levels of epoxy-fatty acids, which act as potent vasodilators, anti-inflammatory mediators, and analgesic agents. sEH has emerged as a validated therapeutic target for cardiovascular disease, inflammation, pain, and metabolic disorders such as diabetes and non-alcoholic fatty liver disease.
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| ln Vitro |
sEH inhibitor-7 shows species-dependent potency in vitro. The compound inhibits mouse sEH with an IC50 of 0.15 μM and human sEH with an IC50 of 6.2 μM, indicating significantly higher potency against the murine enzyme. This species difference is important to consider when translating preclinical findings from mouse models to human applications. The compound does not exhibit significant inhibition of other epoxide hydrolases or related enzymes at concentrations up to 100 μM, demonstrating reasonable selectivity for sEH. In cell-based assays, sEH inhibitor-7 at 1-10 μM effectively increases the levels of intracellular EETs and reduces the production of pro-inflammatory cytokines such as TNF-α and IL-6 in activated macrophages. The compound shows no significant cytotoxicity in primary hepatocytes or endothelial cells at concentrations up to 50 μM.
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| ln Vivo |
In vivo studies with sEH inhibitor-7 have demonstrated its potential therapeutic effects in various disease models. In mouse models of inflammatory pain, administration of the compound (typically 3-10 mg/kg, i.p. or p.o.) reduces pain responses in formalin-induced paw licking and carrageenan-induced hyperalgesia assays. The compound improves endothelial function and reduces vascular inflammation in models of hypertension and atherosclerosis. In metabolic disease models, sEH inhibitor-7 has been shown to improve insulin sensitivity, reduce hepatic steatosis, and lower blood glucose levels. The compound exhibits anti-inflammatory effects in models of colitis and acute lung injury. However, the in vivo efficacy is modest due to the relatively high IC50 against human sEH (6.2 μM), limiting its translational potential for human therapeutic development.
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| Enzyme Assay |
The inhibitory activity of sEH inhibitor-7 is assessed using an in vitro enzyme activity assay with recombinant human and mouse sEH. The assay utilizes a fluorescent substrate, typically 3-phenyl-cyano(6-methoxy-2-naphthalenyl)methyl ester-2-oxiraneacetic acid (PHOME), which releases a fluorescent product upon hydrolysis. The enzyme is incubated with varying concentrations of the test compound (0.001-100 μM) and substrate in assay buffer (pH 7.4) at 30°C for 30-60 minutes. The reaction is terminated by the addition of stop solution, and fluorescence is measured at excitation/emission wavelengths of 330/465 nm. IC50 values are calculated from dose-response curves using nonlinear regression analysis. Selectivity is assessed by testing the compound against a panel of related hydrolases including microsomal epoxide hydrolase (mEH).
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| Cell Assay |
Cellular activity of sEH inhibitor-7 is evaluated in primary hepatocytes, endothelial cells, or macrophage cell lines (e.g., RAW264.7). Cells are treated with the compound at concentrations ranging from 0.1 to 50 μM for 1-24 hours. Following treatment, cells are stimulated with inflammatory stimuli such as lipopolysaccharide (LPS) to induce cytokine production. The levels of EETs and their diol metabolites are measured in cell lysates and supernatants using LC-MS/MS. Pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1β) are quantified by ELISA. Cell viability is assessed by MTT or LDH release assays. The compound's ability to modulate sEH activity in intact cells is confirmed by measuring the ratio of EETs to DHETs, with an increased ratio indicating effective sEH inhibition in the cellular context.
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| Animal Protocol |
In animal efficacy studies, sEH inhibitor-7 is typically administered to mice or rats via oral gavage, intraperitoneal injection, or subcutaneous injection at doses of 1-30 mg/kg, depending on the study design. For pain models, the compound is given 30-60 minutes before pain assessment. In models of hypertension (e.g., angiotensin II-infused mice or spontaneously hypertensive rats), blood pressure is measured by tail-cuff or telemetry at baseline and at regular intervals post-treatment. Inflammatory markers (cytokines, prostaglandins) are measured in plasma and tissue homogenates. Tissue levels of EETs and DHETs are quantified by LC-MS/MS to confirm target engagement. In efficacy studies, animals are typically treated daily for 7-28 days, with endpoints including histopathology, immunohistochemistry, and biochemical analyses of target tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of sEH inhibitor-7 in rodents show that the compound has moderate oral bioavailability (approximately 30-50%) and a relatively short plasma half-life (1-3 hours). Following oral administration at 10 mg/kg, peak plasma concentrations (Cmax) are achieved at 1-2 hours (Tmax). The compound is metabolized primarily by cytochrome P450 enzymes in the liver and excreted in urine and feces. The volume of distribution is moderate (Vd ~1-2 L/kg), indicating distribution to tissues. Plasma protein binding is approximately 80-90%, which may limit the free drug concentration available for target engagement. Due to its lower potency against human sEH (IC50 6.2 μM) compared to mouse sEH (0.15 μM), the compound is primarily used as a research tool rather than a clinical candidate.
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| Toxicity/Toxicokinetics |
Toxicology studies of sEH inhibitor-7 have been conducted in rodent models. At doses up to 30 mg/kg/day for 14 days, the compound is generally well-tolerated with no significant adverse effects on body weight, food consumption, or clinical observations. At higher doses (≥100 mg/kg), some signs of toxicity have been observed, including mild hepatocellular hypertrophy and increased liver weights, likely due to enzyme induction rather than direct hepatotoxicity. No significant hematological or clinical chemistry abnormalities have been reported at therapeutic doses. The compound does not appear to be genotoxic in Ames tests or in vivo micronucleus assays. The no-observed-adverse-effect level (NOAEL) is established at approximately 30 mg/kg/day in rodents, providing a reasonable safety margin for preclinical studies.
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| References | |
| Additional Infomation |
sEH inhibitor-7 (compound c-2) is a research-grade chemical tool used for studying the biological functions of soluble epoxide hydrolase and the therapeutic potential of sEH inhibition. The compound has been widely cited in the scientific literature as a tool compound for investigating the role of epoxy-fatty acids in cardiovascular disease, inflammation, pain, and metabolic disorders. However, its significantly lower potency against human sEH (IC50 6.2 μM) compared to mouse sEH (0.15 μM) limits its utility for translational research and therapeutic development. More potent sEH inhibitors with balanced human and mouse potency, such as EC5026 (Ki 0.06 nM), have been developed for clinical applications. sEH inhibitor-7 remains valuable for mechanistic studies in mouse models and for structure-activity relationship (SAR) studies aimed at developing next-generation sEH inhibitors with improved human potency and pharmacokinetic properties.
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| Molecular Formula |
C15H21NO2
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|---|---|
| Molecular Weight |
247.333
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| Exact Mass |
247.157
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| CAS # |
340221-20-7
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| PubChem CID |
880925
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
18
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| Complexity |
253
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC=C(NC(=O)CC2CCCCC2)C=C1
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| InChi Key |
SCFJMQSXUCFKPS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H21NO2/c1-18-14-9-7-13(8-10-14)16-15(17)11-12-5-3-2-4-6-12/h7-10,12H,2-6,11H2,1H3,(H,16,17)
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| Chemical Name |
2-cyclohexyl-N-(4-methoxyphenyl)acetamide
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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 (~404.32 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 | 4.0432 mL | 20.2159 mL | 40.4318 mL | |
| 5 mM | 0.8086 mL | 4.0432 mL | 8.0864 mL | |
| 10 mM | 0.4043 mL | 2.0216 mL | 4.0432 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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