Darbufelone mesylate (CI-1004 mesylate) inhibited PGF2α and LTB4 in cells and demonstrated IC50 values of 0.19 μM for PGHS-2 and 20 μM for PGHS-1.

PGHS2:0.98 ± 0.03μM(Kd), PGHS2:0.19 μM, PGHS2:10±5 μM(Ki), H520:21μM, PGHS1:20 μM, A549 cells:20μM

Darbufelone, a noncompetitive inhibitor of PGHS-2 with a Ki value of 10±5 μM, exhibits fluorescence quenching of PGHS-2 at 325 nm (λex=280 nm) with a Kd of 0.98±0.03 μM[2].
To assess the putative anti-proliferative effect of Darbufelone, A549, H520, and H460 cell lines derived from three distinct pathological subtypes of non-small cell lung cancer (NSCLC) (adenocarcinoma, squamous, and large cell lung cancer, respectively) are utilized. The cell lines are treated with increasing concentrations of Darbufelone, ranging from 5 to 60 μM, for a duration of 72 hours. The growth inhibition of these three cell lines gradually increases with higher concentrations of the drug. The IC50 values for A549 and H520 are 20±3.6 and 21±1.8 μM, respectively, while H460 exhibits a lower IC50 of 15±2.7 μM[1].

Darbufelone, a dual inhibitor of cellular PGF2R and LTB4 production, exhibits oral activity in animal models of inflammation and arthritis without causing ulcers. When mice were treated with bufafenone at a dose of 80 mg/kg/day, the tumor volume decreased in a time-dependent manner. In contrast, lower doses of bufafenone (20 or 40 mg/kg/day) did not significantly inhibit tumor weight. At necropsy, the tumor weight of mice treated with bufafenone (80 mg/kg/day) was reduced by 30.2% compared to the control group.