| Description | Darbufelone mesylate (CI-1004 mesylate) inhibited PGF2α and LTB4 in cells. Darbufelone mesylate inhibited PGHS-2 with IC50 value of 0.19 μM and PGHS-1 with IC50 value of 20 μM. |
| In vitro | Darbufelone作为PGHS-2的非竞争性抑制剂，其Ki值为10±5 μM，在325 nm（λex=280 nm）处对PGHS-2表现出荧光猝灭现象，Kd值为0.98±0.03 μM[2]。为评估Darbufelone的潜在抗增殖效果，采用来源于非小细胞肺癌(NSCLC)三种不同病理亚型（分别为腺癌、鳞状细胞和大细胞肺癌）的A549、H520和H460细胞系。这些细胞系以5至60 μM不等浓度的Darbufelone处理72小时，随着化合物浓度增加，三种细胞系的生长抑制逐渐升高。A549和H520的IC50值分别为20±3.6和21±1.8 μM，而H460的IC50较低，为15±2.7 μM[1]。 |
| In vivo | Darbufelone 是一种同时抑制细胞内PGF2R和LTB4产生的复合抑制剂，在口服动物炎症和关节炎模型中显现出活性，且不引起溃疡。实验中，小鼠每日口服bufafenone剂量为80 mg/kg时，肿瘤体积呈时间依赖性减小。相对而言，较低剂量的bufafenone（20或40 mg/kg/天）对肿瘤重量的抑制不显著。解剖观察时，接受bufafenone（80 mg/kg/天）治疗的小鼠肿瘤重量比对照组减轻了30.2%。 |
| Target activity | PGHS1:20 μM, PGHS2:0.19 μM, H520:21μM, PGHS2:10±5 μM(Ki), A549 cells:20μM, PGHS2:0.98 ± 0.03μM(Kd) |
| Synonyms | CI-1004 mesylate |
| molecular weight | 428.57 |
| Molecular formula | C19H28N2O5S2 |
| CAS | 139340-56-0 |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 100 mg/mL (233.33 mM), Sonication is recommended. H2O: <0.1mg/mL |
| References | 1. Ye X, et al. Darbufelone, a novel anti-inflammatory drug, induces growth inhibition of lung cancer cells both in vitro and in vivo. Cancer Chemother Pharmacol. 2010 Jul;66(2):277-85. 2. Johnson AR, et al. Slow-binding inhibition of human prostaglandin endoperoxide synthase-2 with darbufelone, an isoform-selective antiinflammatory di-tert-butyl phenol. Biochemistry. 2001 Jun 26;40(25):7736-45. |