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NSC 23766

现货
Catalog No.
A1952
Rac1-GEF相互作用的选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 980.00
现货
5mg
¥ 500.00
现货
25mg
¥ 2,000.00
现货
100mg
¥ 4,800.00
现货

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Background

NSC-23766 is a specific inhibitor of Rac with IC50 of 50μM.

NSC-23766 blocks the activation of Rac 1 through binding the GEFs including Trio and Tiam 1 [1]. In human dermal microvascular endothelial cells, NSC-23766 decreased trans-endothelial electrical resistance and caused the intercellular gap formation. Inhibition of Rac 1 by NSC-23766 shortly reduced endothelial barrier functions as revealed by measurement of TER and the appearance of intracellular gaps [2]. In the mucous cell of the intestine, inhibition of Rac1 either by NSC-23766 protected cells from TNF-α-induced apoptosis by inhibiting caspase-3, -8 and -9 activities. Inhibition of Rac1 significantly prevented TNF-α-induced activation of JNK1/2, but did not modulate TNF-α-induced ERK1/2, Akt and p38 MAPK activity [3].

References:
[1]. Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7618-23.
[2]. Baumer Y, Spindler V, Werthmann RC, Bünemann M, Waschke J. Role of Rac 1 and cAMP in endothelial barrier stabilization and thrombin-induced barrier breakdown. J Cell Physiol. 2009 Sep;220(3):716-26.
[3]. Jin S1, Ray RM, Johnson LR. Rac1 mediates intestinal epithelial cell apoptosis via JNK. Am J Physiol Gastrointest Liver Physiol. 2006 Dec;291(6):G1137-47.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt530.96
Cas No.1177865-17-6
FormulaC24H35N7.3HCl
Solubility≥26.55mg/mL in DMSO
Chemical Name6-N-[2-[5-(diethylamino)pentan-2-ylamino]-6-methylpyrimidin-4-yl]-2-methylquinoline-4,6-diamine
SDFDownload SDF
Canonical SMILESCCN(CC)CCCC(C)NC1=NC(=CC(=N1)NC2=CC3=C(C=C2)N=C(C=C3N)C)C
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]:

Rho GTP酶活性测定

在直径为10 cm的培养皿中,处于对数生长期的细胞经低血清(0.5%血清或其它培养液)饥饿培养24小时后,再使用缓冲液(含20 mM Tris HCl(pH 7.6),100 mM NaCl,10 mM MgCl2,1% Nonidet P-40,10% glycerol以及1 × 蛋白酶抑制剂混合物)将其裂解。分离裂解物,取上清液,使蛋白质浓度归一化。在裂解物中,使用蛋白效应区体外结合实验测定结合了GTP的Rac1。进行His6-PAK1 PBD拉下实验时,将细胞裂解物与琼脂糖(含Ni2+)固定化的His6-PAK1 PBD区(从大肠杆菌中纯化而得)(~ 1 μg)一起孵育30分钟。使用洗涤缓冲液将琼脂糖(含Ni2+)共沉淀物冲洗2次,并使用抗Rac1单克隆抗体进行免疫印迹分析。

细胞实验 [2]:

细胞系

人乳腺癌细胞系MDA-MB-231和MDA-MB-468以及正常乳腺上皮细胞系MCF12A

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℃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℃可放置数月。

反应条件

0 ~ 100 μM;2天

实验结果

NSC 23766抑制细胞生长并诱导其凋亡。NSC 23766呈剂量依赖性地降低MDA-MB-468和MDA-MB-231细胞活力,其IC50值为~ 10 μM,但几乎不影响正常乳腺上皮细胞MCF12A。给予NSC 23766,24小时后,处于G1期的MDA-MB-231细胞增加了41% ~ 65%,而处于S期和G2-M期的细胞相应减少。100μM NSC 23766使MDA-MB-468细胞凋亡增加6倍。

动物实验 [3]:

动物模型

C57BL/6小鼠

给药剂量

2.5 mg/kg;腹腔注射

实验结果

在C57BL/6小鼠,腹腔注射NSC 23766(2.5 mg/kg)。6小时后,循环造血干细胞/祖细胞含量提升了2倍。

其他注意事项

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]. Gao Y1, Dickerson JB, Guo F, Zheng J, Zheng Y. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7618-23.

[2]. Yoshida T, Zhang Y, Rivera Rosado LA, Chen J, Khan T, Moon SY, Zhang B. Blockade of Rac1 activity induces G1 cell cycle arrest or apoptosis in breast cancer cells through downregulation of cyclin D1, survivin, and X-linked inhibitor of apoptosis protein. Mol Cancer Ther. 2010 Jun;9(6):1657-68.

[3]. Akbar H1, Cancelas J, Williams DA, Zheng J, Zheng Y. Rational design and applications of a Rac GTPase-specific small molecule inhibitor. Methods Enzymol. 2006;406:554-65.

生物活性

Description NSC 23766是Rac GTPase的抑制剂,靶向鸟苷酸交换因子(GEFs)诱导的Rac激活,IC50值为50 μM。
靶点 Rac GTPase          
IC50 50 μM          

质量控制

化学结构

NSC 23766