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GSK2801

现货
Catalog No.
B5998
BAZ2A和BAZ2B bromodomains抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 500.00
现货
10mg
¥ 750.00
现货
50mg
¥ 3,050.00
现货

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Background

GSK2801, as an inhibitor of BAZ2A and BAZ2B bromodomains, is potent, selective and cell active acetyl-lysine competitive, with dissociation constants (KD) of 136 and 257 nM for binding to BAZ2B and BAZ2A, respectively [1].

Bromodomains, as protein interaction domains, are acetyl-lysine specific. Bromodomain containing proteins BAZ2A and BAZ2B are closely related. The nucleolar remodeling complex (NoRC) regulates the expression of noncoding RNAs. BAZ2A and BAZ2B constitute the central scaffolding protein of NoRC [1].

In U2OS cells, treatment with the SAHA induced hyperacetylated chromatin. In a GFP-BAZ2A fusion construct, the conserved asparagines that are essential for recognizing the acetylated lysine has been mutated. When a GFP-BAZ2A fusion construct was transfected into SAHA-treated U2OS cells, the mutant construct accelerated FRAP half-recovery time. Treatment with GSK2801 alone in U2OS cells also accelerated FRAP half-recovery time. Both acceleration extents are the same. This meant that GSK2801 can displace BAZ2A from chromatin [1].

Pharmacokinetic parameters of GSK2801 after intraperitoneal and oral dosing to male CD1 mice were measured. Data showed that after oral dosing in vivo, GSK2801 has reasonable exposure, reasonable plasma stability and modest clearance. GSK2801 can be used as an inhibitor of BAZ2A/B bromodomain in vivo [1]. No more in vivo data of the treatment with GSK2801 are found.

Reference:
[1].  Chen P, Chaikuad A, Bamborough P, et al. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. Journal of medicinal chemistry, 2015.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt371.45
Cas No.1619994-68-1
FormulaC20H21NO4S
Solubility≥18.55mg/mL in DMSO
Chemical Name1-(1-(2-(methylsulfonyl)phenyl)-7-propoxyindolizin-3-yl)ethanone
SDFDownload SDF
Canonical SMILESCCCOC(C=CN12)=CC2=C(C3=CC=CC=C3S(C)(=O)=O)C=C1C(C)=O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

U2OS细胞

制备方法

在DMSO中的溶解度大于18.6 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

1 μM;1小时

实验结果

在转染GFP-BAZ2A的U2OS细胞中,GSK2801减少FRAP半恢复时间。其减少量与转染了突变GFP-BAZ2A的U2OS细胞的减少量相同。上述结果表明GSK2801把BAZ2A从染色质中置换出来。

动物实验 [1]:

动物模型

雄性CD1小鼠

给药剂量

30 mg/kg;腹腔注射或口服给药

实验结果

在雄性CD1小鼠中,单次给予GSK2801(30 mg/kg;口服给药)显示出合理的体内暴露量和血浆稳定性,以及适度的清除率 (Tmax = 1.0 hr; Cmax = 435 ng/mL; T1/2 = 1.5 hrs)。上述结果表明GSK2801可以在体内用作BAZ2A/B bromodomain抑制剂。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Chen P, Chaikuad A, Bamborough P, Bantscheff M, Bountra C, Chung CW, Fedorov O, Grandi P, Jung D, Lesniak R, Lindon M, Müller S, Philpott M, Prinjha R, Rogers C, Selenski C, Tallant C, Werner T, Willson TM, Knapp S, Drewry DH. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. J Med Chem. 2016 Feb 25;59(4):1410-24.

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