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BIX 02565

现货
Catalog No.
B1295
RSK2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,750.00
现货
5mg
¥ 2,380.00
现货
10mg
¥ 3,610.00
现货
25mg
¥ 5,230.00
现货
50mg
¥ 8,550.00
现货

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Background

BIX 02565 is a novel inhibitor of ribosomal S6 kinase 2 with IC50 value of 1 nM [1].

Ribosomal S6 kinase (RSK) is a Na/H exchanger (NHE) -activating factor and is important for pH maintenance during the early phase of cellular stress. While, NHE activation leads to Ca2+ overload and cardiac hypertrophy over longer periods [2].

BIX 02565 is a novel RSK2 inhibitor. Also, BIX 02565 inhibited adrenergic ɑ1A-, ɑ1B-, ɑ1D-, ɑ2A-, β2- and imidazoline I2 receptors with IC50 values ranging from 0.052 to 1.820 μM. These receptors played important roles in the regulation of vascular tone and cardiac function [2]. Also, BIX 02565 inhibited LRRK2 and PRKD1 with IC50 values of 16 and 35 nM [1].

In the rat CV screen, BIX 02565 (1, 3 and 10 mg/kg) significantly decreased heart rate (-93 +13 beats/min) and mean arterial pressure (MAP: to -65 +6 mm Hg below baseline). In telemetry-instrumented rats, BIX 02565 (30, 100 and 300 mg/kg for 4 days) reduced MAP (to -39 + 4 mm Hg) in a concentration-dependent way [2].

References:
[1].  Kirrane TM, Boyer SJ, Burke J, et al. Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. Bioorg Med Chem Lett, 2012, 22(1): 738-742.
[2].  Fryer RM, Muthukumarana A, Chen RR, et al. Mitigation of off-target adrenergic binding and effects on cardiovascular function in the discovery of novel ribosomal S6 kinase 2 inhibitors. J Pharmacol Exp Ther, 2012, 340(3): 492-500.

Chemical Properties

StorageStore at -20°C
M.Wt458.56
Cas No.1311367-27-7
FormulaC26H30N6O2
Solubility≥22.95mg/mL in DMSO
SDFDownload SDF
Canonical SMILESC[C@](N12)([H])CCNC(C2=CC3=C1C=C(/C(O)=N/C4=NC5=CC=CC=C5N4CCCN(C)C)C=C3)=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

激酶实验 [1]:

RSK2的IC50测定

评价化合物抑制RSK2对底物肽的磷酸化的能力参考2011年Boyer等人所述。 简言之,使用GloPlus(Promega,Madison,WI)激酶试剂盒中的人类RSK2蛋白(Invitrogen,Carlsbad,CA)测量激酶活性,该试剂盒是基于荧光素-荧光素酶的检测试剂来定量残留的ATP。以发光模式使用384孔在LJL Analyst(Molecular Devices,Sunnyvale,CA)仪器上测量相对光单位信号; 相对光单位信号转化为对照的百分比; 将IC 50拟合到标准四参数对数方程。

动物实验 [1]:

动物模型

大鼠模型

剂量

1、3、10、30、100和300mg / kg,口服。 每天一次,共4天

应用

BIX 02565(1,3和10mg / kg)引起麻醉大鼠的平均动脉压和心率的降低。 此外,遥测仪表的清醒大鼠每日口服一次BIX 02565,BIX 02565(30、100和300mg / kg)也以浓度依赖性降低大鼠平均动脉压(MAP)。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1. Fryer, R. M., Muthukumarana, A., Chen, R. R., Smith, J. D., Mazurek, S. N., Harrington, K. E., Dinallo, R. M., Burke, J., DiCapua, F. M., Guo, X., Kirrane, T. M., Snow, R. J., Zhang, Y., Soleymanzadeh, F., Madwed, J. B., Kashem, M. A., Kugler, S. Z., O'Neill, M. M., Harrison, P. C., Reinhart, G. A. and Boyer, S. J. (2012) Mitigation of off-target adrenergic binding and effects on cardiovascular function in the discovery of novel ribosomal S6 kinase 2 inhibitors. J Pharmacol Exp Ther. 340, 492-500

质量控制

化学结构

BIX 02565