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BS-181 HCl

现货
Catalog No.
A5700
CDK7抑制剂
组合的产品项目
规格价格库存 数量
100mg
¥ 7,500.00
现货
10mM (in 1mL DMSO)
¥ 2,940.00
现货
25mg
¥ 3,000.00
现货
5mg
¥ 1,000.00
现货

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Background

IC50: 21 nm (CDK7)

Normal progression through the cell cycle requires the sequential action of cyclin-dependent kinases CDK1, CDK2, CDK4, and CDK6. Direct or indirect deregulation of CDK activity is a feature of almost all cancers and has led to the development of CDK inhibitors as anticancer agents.BS-181 is a highly selective CDK7 inhibitor with IC50 of 21 nM. ; >40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9.

In vitro: BS-181, inhibited CAK activity with an IC50 of 21 nmol/L. Testing of other CDKs as well as another 69 kinases showed that BS-181 only inhibited CDK2 at concentrations lower than 1 μmol/L, with CDK2 being inhibited 35-fold less potently (IC50 880 nmol/L) than CDK7. In MCF-7 cells, BS-181 inhibited the phosphorylation of CDK7 substrates, promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines [1].

In vivo: BS-181 was stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. The same dose of drug inhibited the growth of MCF-7 human xenografts in nude mice. BS-181 therefore provides the first example of a potent and selective CDK7 inhibitor with potential as an anticancer agent [1].

Clinical trial: BS-181 is currently in the preclinical development and non clinical trial is ongoing.

Reference:
[1] Ali S, Heathcote DA, Kroll SH, Jogalekar AS, Scheiper B, Patel H, Brackow J, Siwicka A, Fuchter MJ, Periyasamy M, Tolhurst RS, Kanneganti SK, Snyder JP, Liotta DC, Aboagye EO, Barrett AG, Coombes RC.  The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res. 2009;69(15):6208-15.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt416.99
Cas No.1397219-81-6
FormulaC22H32N6.HCl
Solubility≥20.85mg/mL in DMSO, ≥6.49 mg/mL in EtOH with ultrasonic, <2.44 mg/mL in H2O
Chemical Name5-N-(6-aminohexyl)-7-N-benzyl-3-propan-2-ylpyrazolo[1,5-a]pyrimidine-5,7-diamine;hydrochloride
SDFDownload SDF
Canonical SMILESCC(C)C1=C2N=C(C=C(N2N=C1)NCC3=CC=CC=C3)NCCCCCCN.Cl
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

激酶实验 [1]:

体外激酶抑制实验

CDK7活性抑制实验的一般步骤如下:将不同浓度的BS-181 HCl与纯化的重组CDK7/CycH/MAT1复合物一起孵育。通过荧光素酶实验测定反应中残留的游离ATP。因此,荧光素酶活性可用于测定CDK7活性,测定其IC50值。

细胞实验 [1]:

细胞系

MCF-7细胞

制备方法

在DMSO中的溶解度大于10 mM。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

50 μM;24小时

实验结果

在MCF-7细胞中,BS-181 HCl抑制CDK7底物磷酸化,同时,促进细胞周期停滞和细胞凋亡,从而抑制癌细胞生长。

动物实验 [1]:

动物模型

MCF-7细胞异种移植小鼠模型

给药剂量

10或20 mg/kg;腹腔注射;每日2次,持续2周

实验结果

在MCF-7细胞异种移植小鼠模型中,BS-181 HCl呈剂量依赖性地抑制肿瘤生长,同时,无明显的毒性。

其它注意事项

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]. Ali S, Heathcote DA, Kroll SH, Jogalekar AS, Scheiper B, Patel H, Brackow J, Siwicka A, Fuchter MJ, Periyasamy M, Tolhurst RS, Kanneganti SK, Snyder JP, Liotta DC, Aboagye EO, Barrett AG, Coombes RC. The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res. 2009;69(15):6208-15.

生物活性

描述 BS-181 HCl是一种高选择性的CDK7抑制剂,IC50值为21 nM。
靶点 CDK7          
IC50 21 nM          

质量控制

化学结构

BS-181 HCl