BAZ2-ICR

CAS号:1665195-94-7
英文名:4-[4-(1-methyl-1H-pyrazol-4-yl)-1-[2-(1-methyl-1H-pyrazol-4-yl)ethyl]-1H-imidazol-5-yl]-benzonitrile
中文名:BAZ2-ICR
CBNumber:CB63054338
分子式:C20H19N7
分子量:357.41
MOL File:1665195-94-7.mol

BAZ2-ICR化学性质

沸点 :632.8±55.0 °C(Predicted)
密度 :1.26±0.1 g/cm3(Predicted)
溶解度 :DMSO:18.58(Max Conc. mg/mL);51.99(Max Conc. mM)
DMF:20.0(Max Conc. mg/mL);55.96(Max Conc. mM)
DMF:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.4(Max Conc. mM)
Ethanol:13.37(Max Conc. mg/mL);37.41(Max Conc. mM)
形态 :A crystalline solid
酸度系数(pKa) :4.29±0.61(Predicted)
颜色 :Off-white to light yellow

BAZ2-ICR性质、用途与生产工艺

生物活性 BAZ2-ICR 是一种有效的，选择性的，具有细胞活性和口服活性的 BAZ2A/B 溴结构域抑制剂，IC50 分别为 130 nM 和 180 nM，Kd 分别为 109 nM 和 170 nM。BAZ2-ICR 结合 BAZ2A/B 的选择性比 CECR2 高 10-15 倍，比其他溴结构域高 100 倍以上。BAZ2-ICR 是一种表观遗传化学探针。
靶点

IC50: 130 nM (BAZ2A) and 180 nM (BAZ2B); Kd: 109 nM (BAZ2A) and 170 nM (BAZ2A)
体外研究

To investigate whether BAZ2-ICR (Compound 13) can displace BAZ2 bromodomains from chromatin in living cells, a fluorescence recovery after photobleaching (FRAP) assay utilizing GFP-tagged BAZ2A full length protein transfected into human osteosarcoma cells (U2OS) are tested. 1 μM BAZ2-ICR reduces the recovery time of the wild-type (wt) construct to a level similar to the dominant negative mutant, confirming that BAZ2-ICR inhibits BAZ2A in cells.
体内研究

BAZ2-ICR (Compound 13) shows very high solubility (25 mM in D2O), a measured log D of 1.05, high stability in mouse microsomes, and permeation in the CaCo-2 model and thus a suitable profile for oral and intravenous gavage. BAZ2-ICR (5 mg/kg) shows 70% bioavailability and moderate clearance (∼50% of mouse liver blood flow) and volume of distribution.