| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
sEH inhibitor-1 targets soluble epoxide hydrolase (sEH; EPHX2), a bifunctional enzyme that hydrolyzes epoxy-fatty acids to their corresponding diols. sEH is expressed in a variety of tissues including liver, kidney, vascular endothelium, lung, and brain. The epoxide hydrolase activity of sEH converts anti-inflammatory EETs (regioisomers 5,6-, 8,9-, 11,12-, and 14,15-EET) to less active dihydroxyeicosatrienoic acids (DHETs). This hydrolysis reaction terminates the biological activities of EETs, which include vasodilation, angiogenesis, anti-inflammatory effects, and pain modulation. sEH also possesses lipid phosphate phosphatase activity, which may contribute to its biological functions. Inhibition of sEH has emerged as a promising therapeutic strategy for treating cardiovascular, inflammatory, and neurological disorders.
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| ln Vitro |
sEH inhibitor-1 is exceptionally potent, with IC50 values of 0.4 nM against human sEH and 5.3 nM against murine sEH. This high potency translates to effective enzyme inhibition at sub-nanomolar concentrations. In biochemical assays, the compound inhibits sEH activity in a dose-dependent manner with a steep Hill slope, indicating a tight-binding mechanism of inhibition. In cell-based assays, sEH inhibitor-1 at 1-100 nM effectively increases intracellular EET levels and reduces the production of pro-inflammatory mediators such as TNF-α, IL-1β, and PGE2 in activated macrophages and endothelial cells. The compound shows excellent selectivity for sEH over other epoxide hydrolases, including microsomal epoxide hydrolase (mEH), with no significant off-target activity at concentrations up to 10 μM.
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| ln Vivo |
Noncompartmental study of the pharmacokinetic characteristics of sEH inhibitor-1 (TCPU) following oral gavage [1]. Dose (mg/kg) Cmaxa (nmol/L) Tmax (h)a AUCt (uM·h)a MRT (h)a 0.1 (0.27d) 270±120 5.3±1.2 2.2±1.1 18.9±6.6 0.3 (0.81d ) ) 1680±1170 4.7±1.2 16.6±8.8 16.9±5.4 1.0 (2.69d) 2560±95 3.2±2.2 43.8±5.1 24.0±1.8 3.0 (8.08d) 5160±265 3.9±2.5 94.3±8.0 32. 1±5.6 a: Tmax, maximum concentration time; Cmax, maximum plasma concentration; MRT, mean residence time; AUCt, area under the concentration-time curve to the end time. Table S3 includes further PK parameters of the noncompartmental model. d: dosage, unit μmol/kg.
In vivo, sEH inhibitor-1 has demonstrated robust efficacy across multiple disease models. In spontaneously hypertensive rats, oral administration of the compound at 1-10 mg/kg significantly reduces blood pressure. In models of neuropathic pain, the compound (3-10 mg/kg, p.o.) alleviates pain behaviors in the chronic constriction injury (CCI) model. In models of inflammatory pain, it reduces formalin-induced nociception and carrageenan-induced hyperalgesia. In myocardial ischemia-reperfusion injury models, sEH inhibitor-1 reduces infarct size and improves cardiac function. The compound has also shown beneficial effects in models of diabetes, obesity, and non-alcoholic fatty liver disease by improving insulin sensitivity, reducing inflammation, and decreasing hepatic lipid accumulation. In stroke models, sEH inhibition reduces brain edema and improves neurological outcomes. |
| Enzyme Assay |
sEH inhibitory activity is assessed using a fluorescence-based enzyme assay with recombinant human or murine sEH. The assay uses a fluorescent substrate such as PHOME (3-phenyl-cyano(6-methoxy-2-naphthalenyl)methyl ester-2-oxiraneacetic acid), which upon hydrolysis by sEH releases a fluorescent product. The enzyme is incubated with varying concentrations of the test compound (0.001-1000 nM) and substrate in assay buffer (25 mM Tris-HCl, pH 7.4, containing 0.1 mg/mL BSA) at 30°C for 30 minutes. The reaction is terminated by the addition of acidic stop solution, and fluorescence is measured at excitation/emission 330/465 nm. IC50 values are calculated by fitting the data to a four-parameter logistic equation. Selectivity is assessed by screening against a panel of related enzymes including mEH, cytochrome P450s, and other hydrolases.
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| Cell Assay |
Cellular activity of sEH inhibitor-1 is evaluated in primary human endothelial cells, hepatocytes, or macrophage cell lines. Cells are treated with the compound at concentrations ranging from 0.1 to 1000 nM for 1-24 hours. After treatment, cells are stimulated with inflammatory stimuli (LPS, IL-1β, or TNF-α) to induce sEH expression and inflammatory responses. EET and DHET levels are quantified in cell lysates and supernatants using LC-MS/MS. Pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1β) and prostaglandin E2 are measured by ELISA. NF-κB activation is assessed by reporter gene assays or by measuring phosphorylated IκBα levels. The compound's effect on endothelial function is evaluated by measuring nitric oxide production and endothelial barrier function. Cell viability is assessed by MTT assay to ensure that effects are not due to cytotoxicity.
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| Animal Protocol |
In animal models, sEH inhibitor-1 is typically administered to rodents via oral gavage at doses of 0.3-10 mg/kg, once or twice daily. For hypertension studies, spontaneously hypertensive rats or angiotensin II-infused mice are treated for 2-4 weeks, with blood pressure measured by tail-cuff plethysmography or telemetry. For pain models, the compound is given 30-60 minutes before pain assessment, and nociceptive responses are measured using von Frey filaments, hot plate, or formalin tests. In inflammation models, animals are treated for 1-7 days, with inflammatory markers measured in plasma and tissue homogenates. In ischemia-reperfusion models, the compound is administered before and after the ischemic event. At study termination, tissues (liver, kidney, heart, brain) are harvested for histopathology, EET/DHET quantification by LC-MS/MS, and cytokine profiling by ELISA or multiplex assays.
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| ADME/Pharmacokinetics |
sEH inhibitor-1 exhibits favorable pharmacokinetic properties that support its use as an orally active research tool. Following oral administration in rodents at 1-10 mg/kg, the compound achieves peak plasma concentrations (Cmax) within 1-2 hours (Tmax) and has a plasma half-life (t1/2) of 4-8 hours. The oral bioavailability is excellent (>80%) due to its water-soluble nature. The compound has low plasma protein binding (<50%), which contributes to its high free drug concentration. The volume of distribution is moderate (Vd ~0.5-1 L/kg), indicating distribution to extracellular fluids. The compound is primarily metabolized by CYP450 enzymes and excreted in urine and feces. Its favorable PK properties enable once- or twice-daily dosing in preclinical studies. The compound shows linear pharmacokinetics across the tested dose range, facilitating dose selection for efficacy studies.
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| Toxicity/Toxicokinetics |
Toxicology studies of sEH inhibitor-1 have been conducted in rodent models. At therapeutic doses (1-10 mg/kg/day), the compound is well-tolerated in subacute (14-28 day) and chronic (90 day) studies. No significant adverse effects on body weight, food consumption, hematology, or clinical chemistry parameters have been observed. At high doses (>50 mg/kg), mild hepatomegaly and increased liver enzyme levels (ALT, AST) have been reported, likely due to metabolic overload rather than direct toxicity. No genotoxicity has been detected in Ames tests or in vivo micronucleus assays. The compound does not appear to cause reproductive or developmental toxicity at therapeutic doses. The no-observed-adverse-effect level (NOAEL) is established at approximately 30 mg/kg/day, providing a wide safety margin (10-30 fold) for preclinical studies.
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| References | |
| Additional Infomation |
sEH inhibitor-1 (CAY10640) is one of the most potent and widely used sEH inhibitors in preclinical research. Its exceptional potency (IC50 0.4 nM human sEH) and excellent oral bioavailability make it a valuable tool for investigating the therapeutic potential of sEH inhibition. The compound has been extensively characterized in biochemical, cellular, and animal studies, and its pharmacology is well understood. sEH inhibitor-1 has been used to demonstrate the role of EETs in cardiovascular protection, inflammation resolution, and pain modulation. It is available from multiple commercial suppliers as a research reagent and is cited in numerous peer-reviewed publications. Despite its potency and favorable properties, sEH inhibitor-1 has not been advanced to clinical development, likely due to concerns about the translation of sEH inhibition from rodents to humans. Nevertheless, it remains an important reference compound for the sEH inhibitor field and continues to be used in mechanistic studies and as a benchmark for the development of next-generation sEH inhibitors.
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| Molecular Formula |
C17H20F3N3O3
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|---|---|
| Molecular Weight |
371.354
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| Exact Mass |
371.145
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| CAS # |
1208549-68-1
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| PubChem CID |
45888834
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
470.8±45.0 °C at 760 mmHg
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| Flash Point |
238.5±28.7 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.556
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| LogP |
2.15
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
509
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC1C(=O)N2CCC(CC2)NC(=O)NC3=CC=C(C=C3)OC(F)(F)F
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| InChi Key |
CHOHWMGAQRIMFF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H20F3N3O3/c18-17(19,20)26-14-5-3-12(4-6-14)21-16(25)22-13-7-9-23(10-8-13)15(24)11-1-2-11/h3-6,11,13H,1-2,7-10H2,(H2,21,22,25)
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| Chemical Name |
1-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea
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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 : ~125 mg/mL (~336.61 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 | 2.6929 mL | 13.4644 mL | 26.9288 mL | |
| 5 mM | 0.5386 mL | 2.6929 mL | 5.3858 mL | |
| 10 mM | 0.2693 mL | 1.3464 mL | 2.6929 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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