GSK2801

Research use only, not for human use.

GSK2801 is an effective, specific and cell active acetyl-lysine competitive inhibitor of BAZ2A(Kd: 136 nM) and BAZ2B(Kd: 257 nM) bromodomains.

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