GSK2801

中文名称:

GSK2801

中文同义词:

1-[1-[2-(甲基磺酰基)苯基]-7-丙氧基-3-吲哚嗪基]乙酮;BAZ2A和BAZ2B抑制剂(GSK2801);1-(1-(2-(甲磺酰)苯基)-7-丙氧基吲哚嗪-3-基)乙酮

英文名称:

GSK 2801

英文同义词:

GSK 2801;GSK2801;GSK-2801;1-(7-(2-Methylsulfonyl-phenyl)-4-propoxy-1-aza-bicyclo[4.3.0]nona-2,4,6,8-tetraen-9-yl)-ethanone;1-(1-(2-(methylsulfonyl)phenyl)-7-propoxyindolizin-3-yl)ethanone;1-[1-[2-(Methylsulfonyl)phenyl]-7-propoxy-3-indolizinyl]ethanone;GSK2801 GSK-2801;1-[1-(2-Methanesulfonyl-phenyl)-7-propoxy-indolizin-3-yl]-ethanone

CAS号:

1619994-68-1

分子式:

C20 H21 N O4 S

分子量:

371.45

EINECS号:

相关类别:

小分子抑制剂;小分子抑制剂，天然产物;细胞生物学试剂;Inhibitors

Mol文件:

1619994-68-1.mol

密度 

1.23±0.1 g/cm3(Predicted)

储存条件 

-20°C

生物活性

GSK2801 是一种有效的，选择性的，口服活性的和细胞活性的乙酰赖氨酸竞争性 BAZ2A 和 BAZ2B 溴结构域抑制剂，Kd 值分别为 136 nM 和 257 nM。GSK2801 对 BAZ2A/B 的选择性是 BRD4 的 50 倍以上。

靶点

Kd: 136 nM (BAZ2A) and 257 nM (BAZ2B)

体外研究

GSK2801 binds TAF1L(2) with an affinity K B of 0.31μM (K D : 3.2 μM) and a binding enthalpy change ΔH of −8.6 kcal/mol. ITC experiments using the bromodomain of BRD9 results in the determination of an affinity K B of 0.826 μM (K D : 1.1 μM) and ΔH of −9.8 kcal/mol. GSK2801 or RNAi knockdown of BAZ2A/B with JQ1 selectively displaced BRD2 at promoters/enhancers of ETS-regulated genes. In 2D cultures, enhances displacement of BRD2 from chromatin by combination drug treatment induced senescence. In spheroid cultures, combination treatment induces cleaved caspase-3 and cleaved PARP characteristic of apoptosis in tumor cells. Thus, GSK2801 blocks BRD2-driven transcription in combination with BET inhibitor and induces apoptosis of TNBC.

体内研究

In order to determine the suitability of GSK2801 for in vivo experiments, pharmacokinetic parameters after intraperitoneal and oral dosing to male CD1 mice is measured. GSK2801 has reasonable in vivo exposure after oral dosing, modest clearance, and reasonable plasma stability.

危险品标志 

Xn

危险类别码 

22