| 名稱 | I-BET151 |
| 描述 | I-BET151 (GSK1210151A) (GSK1210151A) is a specific BET inhibitor for BRD2/3/4 (IC50: 0.5/0.25/0.79 μM, in cell-free assays). |
| 細(xì)胞實驗 | 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) |
| 激酶實驗 | 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). |
| 體外活性 | I-BET151（30 mg/kg/day）處理小鼠,可使鼠類MLL-AF9和人類MLL-AF4白血病腫瘤生長受到明顯抑制,顯著增加壽命. |
| 體內(nèi)活性 | 作用于HL60核提取物時, I-BET151（0.5或5 μM）抑制BETs(BRD2/3/4/9)而非23種其他溴區(qū)蛋白結(jié)合到乙?；慕M蛋白肽。I-BET151對含不同 MLL融合的細(xì)胞系均有較強(qiáng)抑制效果,如MV4;11, RS4;11, MOLM13和NOMO1細(xì)胞（IC50：15-192 nM）。I-BET151對多種不同蛋白類型均有較好的選擇性抑制作用,如COX-2,P450,Aurora B,GSK3β,PI3K-γ,GPCR,離子通道及轉(zhuǎn)運(yùn)體。與I-BET762 (GSK525762A)類似,I-BET151 對BRD2/3/4具有的結(jié)合親和力較高（Kd：0.02-0.1 μM）,作用于人類外周血單核細(xì)胞和全血及大鼠WB時,對脂多糖刺激的IL-6細(xì)胞因子產(chǎn)生有顯著抑制作用（IC50：0.16/1.26/1.26 μM）。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 50 mg/mL (120.35 mM)
|
| 關(guān)鍵字 | I-BET-151 | I BET151 | inhibit | bromodomain | BET | Epigenetic Reader Domain | BRD2 | Inhibitor | BRD4 | I-BET 151 | BRD3 | I-BET151 | IBET151 |
| 相關(guān)產(chǎn)品 | Bisdemethoxycurcumin | dBET6 | 3-methyl-1,2,3,4-tetrahydroquinazolin-2-one | CeMMEC1 | (+)-JQ-1 | Curcumin | Naphthol AS-E | J-147 | ABBV-744 | Piflufolastat | Hexamethylene bisacetamide | Anacardic Acid |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 染色質(zhì)修飾分子庫 | 組蛋白修飾化合物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | 干細(xì)胞分化化合物庫 | PPI抑制劑庫 | 細(xì)胞重編程化合物庫 |