COX-2/sEH-IN-1

COX-2/sEH-IN-1 (Compound 9c) is an orally active, dual COX-2 and sEH (soluble epoxide hydrolase) inhibitor with IC50 values of 1.24 µM and 0.40 nM against COX-2 and sEH, respectively. COX-2/sEH-IN-1 shows improved anti-inflammatory activity and highly reduced cardiovascular risks[1].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Immunology/Inflammation >> COX

COX-2:1.24 μM (IC50)

COX-1:8.72 μM (IC50)

sEH:0.40 nM (IC50)

COX-2/sEH-IN-1 (Compound 9c) (10 mg/kg; p.o.; once) exhibits analgesic activity[1]. COX-2/sEH-IN-1 (50 mg/kg; p.o.; once) shows high anti-inflammatory activity[1]. COX-2/sEH-IN-1 (100 mg/kg; p.o.; 2 weeks) affords a perfect cardio-protection and less cardiovascular liabilities[1]. Animal Model: Albino mice (20-30 g)[1] Dosage: 10 mg/kg Administration: Oral administration, once Result: Exhibited analgesic activity with 65.67% inhibition in the number of writhing. Animal Model: Albino rats (120-150 g), carrageenan-induced paw edema model[1] Dosage: 50 mg/kg Administration: Oral administration, once Result: Showed high anti-inflammatory activity with edema inhibition of 64.06%, 95.82%, and 98.15% at 1, 3, 5 h, respectively. Animal Model: Adult male albino Wister rats (170-200 g)[1] Dosage: 100 mg/kg Administration: Oral administration, 2 weeks Result: Exhibited a significant lowering in Troponine-I, LDH and CK-MB levels when compared to celecoxib treated group. Showed remarkably decrease in TNF-α concentration compared to the celecoxib induced cardio-toxicity group. Restored heart GSH level and significantly increased PGI2 level compared to celecoxib group. Showed mild decongestant and mild edema on cardiac blood vessels and showed more or less normal muscle bundles.

[1]. Ahmed H Abdelazeem, et al. Discovery of novel urea-diarylpyrazole hybrids as dual COX-2/sEH inhibitors with improved anti-inflammatory activity and highly reduced cardiovascular risks. Eur J Med Chem. 2020 Nov 1;205:112662.