I-BET151 是 BRD2/3/4 的特异性 BET 抑制剂，IC50值分别为0.5、0.25、0.79 μM。

I-BET151 (GSK1210151A) is a specific BET inhibitor for BRD2/3/4 (IC50: 0.5/0.25/0.79 μM, in cell-free assays).

I-BET151（30 mg/kg/day）处理小鼠,可使鼠类MLL-AF9和人类MLL-AF4白血病肿瘤生长受到明显抑制,显著增加寿命.

作用于HL60核提取物时, I-BET151（0.5或5 μM）抑制BETs(BRD2/3/4/9)而非23种其他溴区蛋白结合到乙酰化的组蛋白肽。I-BET151对含不同 MLL融合的细胞系均有较强抑制效果,如MV4;11, RS4;11, MOLM13和NOMO1细胞（IC50：15-192 nM）。I-BET151对多种不同蛋白类型均有较好的选择性抑制作用,如COX-2,P450,Aurora B,GSK3β,PI3K-γ,GPCR,离子通道及转运体。与I-BET762 (GSK525762A)类似,I-BET151 对BRD2/3/4具有的结合亲和力较高（Kd：0.02-0.1 μM）,作用于人类外周血单核细胞和全血及大鼠WB时,对脂多糖刺激的IL-6细胞因子产生有显著抑制作用（IC50：0.16/1.26/1.26 μM）。

Fluorescence anisotropy (FP) ligand displacement assay: All components are dissolved in buffer of composition 50 mM HEPES pH 7.4, 150 mM NaCl and 0.5 mM CHAPS with final concentrations of BRD 2/3/4 75 nM, fluorescent ligand 5 nM. 10 μL of this reaction mixture is added using a micro multidrop to wells containing 100 nL of various concentrations of I-BET151 or DMSO vehicle (1% final) in Greiner 384 well Black low volume microtitre plate and equilibrated in the dark for 60 minutes at room temperature. Fluorescence anisotropy is read in Envision (lex = 485 nm, lEM = 530 nm; Dichroic = 505 nM).

Cells are exposed to various concentrations of I-BET151 for 24 or 72 hours in 384-well or 96-well plates. For cell growth inhibition assays, plates are added with CellTiter-Glo reagent using a volume equivalent to the cell culture volume in the wells, shaken for approximately 2 minutes and chemiluminescent signal is read on the Analyst GT or EnVision Plate Reader. For cell proliferation assays, CellTiter-Aqueous One is added to each well and plates are incubated for 4 hours at 37 °C. Absorbance is read at 490 nm on a SpectraMax Gemini reader (Only for Reference)

1300031-49-5

C23H21N5O3

415.453

GSK1210151A

DMSO:199.8 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years