GSK2801

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GSK2801 是一种有效、特异性和细胞活性的 BAZ2A(Kd: 136 nM) 和 BAZ2B(Kd: 257 nM) 溴结构域乙酰赖氨酸竞争性抑制剂。

GSK2801 is a A Selective Chemical Probe for BAZ2B/A bromodomains. BAZ2A/B belong to a family of ubiquitously expressed bromodomain containing proteins. Proteins of the BAZ family are characterized by a carboxy-terminal bromodomain adjacent to a PHD finger and a WACZ motif. In addition four other conserved motifs are typically found in the N-terminus of BAZ family members, namely the LH motif (a leucine-rich helical domain), the ZB2 motif and the BAZ 1 and BAZ 2 motifs. Little is known about the biological function of BAZ2B but it has been suggested to regulate nucleosome mobilization by the ATP-dependent chromatin remodeling factor ISWI.

GSK2801 binds TAF1L(2) with an affinity KB of 0.31μM (KD: 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 KB of 0.826 μM (KD: 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.

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.

GSK2801 | GSK-2801 | GSK 2801

Tyrosine Kinase

TAM Receptor

BAZ2A| BAZ2B

Others-Field

——

1619994-68-1

371.45

C20H21NO4S

>98% (HPLC)

DMSO : 50 mg/mL. 134.61 mM; H2O : < 0.1 mg/mL

CCCOc1cc2c(cc(n2cc1)C(=O)C)c1ccccc1S(=O)(=O)C

1-(1-(2-(methylsulfonyl)phenyl)-7-propoxyindolizin-3-yl)ethanone

(-20℃)

With Ice Pack

≥ 2 years