(5Z)-2-氨基-5-[(4-羟基-3,5-二叔丁基苯基)亚甲基]-1,3-噻唑-4-酮

IC50: 0.19 μM (PGHS-2), 20 μM (PGHS-1)

Darbufelone is a noncompetitive inhibitor of PGHS-2 (K _i =10±5 μM). Darbufelone quenches the fluorescence of PGHS-2 at 325 nm (lambda(ex)=280 nm) with K _d =0.98±0.03 μM.To test the putative anti-proliferative effect of Darbufelone, A549, H520 and H460 cell lines are used, which are established from three distinct pathological subtypes of NSCLC (adenocarcinoma, squamous and large cell lung cancer respectively). Increasing concentrations of Darbufelone, ranging from 5 to 60 μM, are tested for 72 h. The cell growth inhibition of these three cell lines gradually increases with higher drug concentration. The IC ₅₀ of A549 and H520 are 20±3.6 and 21±1.8 μM, respectively, while the H460 has much lower IC ₅₀ (15±2.7 μM).

Darbufelone is a dual inhibitor of cellular PGF2R and LTB4 production. Darbufelone is orally active and nonulcerogenic in animal models of inflammation and arthritis. When mice are treated with Darbufelone at dosage of 80 mg/kg/day, the tumor volumes decrease in a time-dependent manner. In contrast, lower dose of Darbufelone (20 or 40 mg/kg/day) dos not show any significant inhibition of tumor weight. At necropsy, the tumor weight in mice treated with Darbufelone (80 mg/kg/day) is reduced by 30.2% in comparison with control group.