sEH-IN-24
sEH-IN-24 is an orally active soluble epoxide hydrolase (sEH) inhibitor with an IC50 of 1.9 nM. sEH-IN-24 inhibits the pro-inflammatory cytokines TNF-α and IL-6. sEH-IN-24 exhibits anti-inflammatory effects and exerts analgesic activity in vivo. sEH-IN-24 prevents pancreatic edema, inflammation and parenchymal atrophy. sEH-IN-24 can be used for the research of acute pancreatitis.
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- CAS No.: 3121405-85-1
- Formule: C28H39NO6
- Masse moléculaire:485.61
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
Description
IC50 & Target
[1]|
IL-6 |
sEH 1.9 nM (IC50) |
In Vitro
sEH-IN-24 (Compound (+)-34) (0.46-1000 nM) potently inhibits sEH with an IC50 of 1.9 nM. It forms stable interactions with key active site residues and maintains dynamic stability when forming a complex with this enzyme[1].
sEH-IN-24 exhibits low cytotoxicity against the normal cell lines 293-T, HL7702 and MIHA, with a GI50 value >100 μM[1].
sEH-IN-24 (0.25-8 μM) potently inhibits LPS-induced release of IL-6 and TNF-α in RAW 264.7 and THP-1 macrophages, with IC50 values ranging from 0.7 to 1.3 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
sEH-IN-24 (5-10 mg/kg; p.o.; single dose) demonstrates potent, dose-dependent oral analgesic activity in a mouse acetic acid-induced writhing model, reducing writhing episodes by 45% at the 10 mg/kg dose[1].
sEH-IN-24 (10 mg/kg; i.p.; two doses at 0.5 h and 2.5 h post-first cerulein injection) exerts robust therapeutic activity in a mouse cerulein-induced acute pancreatitis model, reducing pancreatic histopathology scores by 56.3%, lowering pro-inflammatory cytokines, and increasing anti-inflammatory EET/DHET ratios in pancreatic tissue and plasma[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 23−25 g, 6−8 weeks old)[1]
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Dosage:20 mg/kg (p.o.); 10 mg/kg (p.o.); 10 mg/kg (i.p.); 5 mg/kg (i.p.)
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Administration:p.o.; single dose; i.p.; single dose
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Result:Achieved a paw edema inhibition rate of 37.3% at 2 h post-administration, which remained stable at 31.6% 4 h post-peak efficacy.
Increased plasma 8,9-EET/DHET by 219% and 14,15-EET/DHET by 274% relative to the model group, alongside elevations in 8,9-EET (81.1%) and 14,15-EET (108%) levels, and reductions in 8,9-DHET (17.3%) and 14,15-DHET (23.9%) levels at 20 mg/kg (p.o.).
Increased plasma 8,9-EET/DHET by 315%, 11,12-EET/DHET by 198%, and 14,15-EET/DHET by 308% relative to the model group, alongside elevations in 8,9-EET (56.8%), 11,12-EET (60.4%), and 14,15-EET (121%) levels, and reductions in 8,9-DHET (50.0%), 11,12-DHET (18.9%), and 14,15-DHET (28.2%) levels at 10 mg/kg (i.p.).
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Animal Model:C57BL/6J (male, 23−25 g, 6−8 weeks old)[1]
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Dosage:10 mg/kg; 5 mg/kg
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Administration:p.o.; single dose
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Result:Reduced the number of writhing episodes by 45% relative to the model group at 10 mg/kg (p.o.).
Significantly reduced writhing episodes at 5 mg/kg (p.o.), with activity showing a concentration-dependent correlation.
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Animal Model:C57BL/6J (male, 23−25 g, 6−8 weeks old)[1]
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Dosage:10 mg/kg
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Administration:i.p.; two doses at 0.5 h and 2.5 h post-first cerulein injection
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Result:Reduced total pancreatic histopathological scores by 56.3% relative to the model group, alleviating edema, inflammatory infiltration, and parenchymal atrophy.
Reduced plasma TNF-α levels by 46.8% and IL-6 levels by 67.1% relative to the model group.
Increased pancreatic tissue 8,9-EET/DHET by 424%, 11,12-EET/DHET by 1476%, and 14,15-EET/DHET by 2180% relative to the model group.
Increased plasma 11,12-EET/DHET by 86% and 14,15-EET/DHET by 111% relative to the model group.
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Animal Model:C57BL/6J (male, 8 weeks old)[1]
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Dosage:20 mg/kg
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Administration:p.o.; single dose
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Result:Achieved a plasma Cmax of 10,127 ng/mL and AUC0-24h of 148,683 h·ng/mL.
Achieved a liver Cmax of 36,378 ng/g and AUC0-24h of 468,142 h·ng/g.
Achieved a kidney Cmax of 27,061 ng/g and AUC0-24h of 306,849 h·ng/g.
Achieved a brain Cmax of 1021 ng/g and AUC0-24h of 9127 h·ng/g.
Tissue-to-plasma Cmax ratios were 3.59 (liver), 2.67 (kidney), and 0.101 (brain).
Tissue-to-plasma AUC0-24h ratios were 3.15 (liver), 2.06 (kidney), and 0.061 (brain).
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Animal Model:Sprague-Dawley (SD) (male, 200 g)[1]
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Dosage:20 mg/kg (p.o.); 5 mg/kg (i.v.)
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Administration:p.o.; single dose; i.v.; single dose
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Result:After oral administration, had a Tmax of 2.08 h, Cmax of 2064 ng/mL, AUC0-24h of 17834 h·ng/mL, half-life of 2.38 h, volume of distribution of 4017 mL/kg, systemic clearance of 1308 mL/h/kg, and bioavailability of 22.1%.
After intravenous administration, had a Tmax of 0.09 h, Cmax of 7985 ng/mL, AUC0-24h of 20144 h·ng/mL, half-life of 2.21 h, volume of distribution of 896 mL/kg, and systemic clearance of 273 mL/h/kg.
Chemical Information
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CAS No. 3121405-85-1
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Masse moléculaire 485.61
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Formule C28H39NO6
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SMILES
CC([C@@H]1C2=C(OC3=C1C(C(C)(C(C3(C)C)=O)C)=O)C=C(C=C2OCCCN4CCOCC4)OC)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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LPS-Induced Endotoxemia/Systemic Inflammation
Lipopolysaccharide (LPS)-induced endotoxemia is a widely used in vivo model of acute systemic inflammation in which LPS, a Gram-negative bacterial endotoxin, activates innate immune signaling primarily through TLR4, leading to rapid and transient induction of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and tissues. This cytokine surge is commonly used as a measurable readout of systemic inflammatory activation and immune dysregulation, and is typically assessed within hours after intraperitoneal LPS administration in mouse models of endotoxemia. The model captures key features of systemic inflammatory response syndrome, including cytokine release, immune cell activation, and downstream tissue responses, and has been used to evaluate anti-inflammatory interventions such as cytokine modulation, lipid mediators, and immune cell-targeting therapies.
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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