PFI-1 (PF-6405761), a specific BET (bromodomain-containing protein) inhibitor for BRD4, is with the IC50 of 0.22 μM in a cell-free assay.

BRD4:0.22 μM

在大鼠中,PFI-1 （1 mg/kg）静脉注射,分布体积为1 L/kg, 每分钟的血浆清除率为18mL/kg,半衰期为1小时.PFI-1（2 mg/kg）口服,有效性低至32%;PFI-1 (2 mg/kg)剂量皮下注射给药小鼠,Cmax 为58 ng/mL,Tmax 为1小时,半衰期约为2 小时.

在经脂多糖刺激的人血单核细胞中,PFI-1(EC50=1.89 μM) 抑制细胞产生的IL-6。在三种NET细胞系（胰腺NET衍生的Bon-1,和肺NET衍生的H727和H720）中,PFI-1抑制细胞增殖。在T4302 CD133+细胞中,PFI-1以剂量依赖的方式诱导细胞活力降低。PFI-1 （KD=49 μM）与cAMP反应结合元件结合蛋白结合。

To determine dose response, cells are aliquoted into 96-well plate at 5 × 103 cells per well in triplicates. PFI-1 is added by 2- or 4-fold serial dilutions. Cell number is measured 5 days after plating using the CellTiter-Glo Kit and normalized to corresponding vehicle-treated groups. IC50 values are calculated by the GraphPad Prism 5 software using the 4-parameter logistic nonlinear regression model. To calculate the relative growth of cells, averaged cell titers of each group on day 1 are assigned a value of 1. All subsequent cell titer values are normalized accordingly. (Only for Reference)