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H 89 2HCl

现货
Catalog No.
B2190
PKA抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 650.00
现货
10mg
¥ 630.00
现货
50mg
¥ 2,170.00
现货
200mg
¥ 6,160.00
Ship with 10-15 days

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Background

H 89 2HCl is a potent PKA inhibitor. In a cell-free assay, the Ki of H 89 is 48 nM, 10-fold selective for PKA than PKG and 500-fold greater selectivity than PKC, MLCK, calmodulin kinase II and casein kinase I/II [1].

In vitro:In PC12D cells, pretreatment with H-89 dose-dependently inhibited the forskolin-induced protein phosphorylation, with no influence in intracellular cyclic AMP levels. In PC12D cells, H-89 significantly inhibited the forskolin-induced neurite outgrowth. In PC12D cells, pretreatment with H-89 (30 μM) strikingly inhibited cAMP-dependent histone IIb phosphorylation activity in cell lysates while showed no effects on other protein phosphorylation activity such as cGMP-dependent histone IIb phosphorylation activity [1]. H 89 was a potent and selective PKA inhibitor with Ki of 48 nM in a cell-free assay [2]. H89 also inhibited S6K1, MSK1, PKA, ROCKII, PKBα and MAPKAP-K1b kinases with IC50 of 80, 120, 135, 270, 2600 and 2800 nM, respectively [2]. In the hypotonic medium, 50 μM H89, a concentration commonly used to inhibit PKA, prevented the redistribution response. In normal medium, H89 (50 Μm) induced the redistribution of ERGIC 53 to the ER by 20 min [3].

References:

[1]. Chijiwa T, Mishima A, Hagiwara M, et al. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells[J]. Journal of Biological Chemistry, 1990, 265(9): 5267-5272.

[2]. Lochner A, Moolman J A. The many faces of H89: a review[J]. Cardiovascular drug reviews, 2006, 24(3‐4): 261-274.

[3]. Lee T H, Linstedt A D. Potential role for protein kinases in regulation of bidirectional endoplasmic reticulum-to-Golgi transport revealed by protein kinase inhibitor H89[J]. Molecular biology of the cell, 2000, 11(8): 2577-2590

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文献引用

1. JianHanaWan, ShuHongac, et al. "The regulation of melanocyte-stimulating hormone on the pigment granule dispersion in the xanthophores and melanophores of the large yellow croaker (Larimichthys crocea)." Aquaculture. Available online 2 April 2019.
2. MXinwei Feng, Junfeng Lu, et al. "Mycobacterium smegmatis Induces Neurite Outgrowth and Differentiation in an Autophagy-Independent Manner in PC12 and C17.2 Cells." Front. Cell. Infect. Microbiol., 19 June 2018.
3. Matos, Steven Cordeiro, et al. "Peripheral Neuropathy Induces HCN Channel Dysfunction in Pyramidal Neurons of the Medial Prefrontal Cortex." The Journal of Neuroscience 35.38 (2015): 13244-13256. PMID:26400952

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt519.28
Cas No.130964-39-5
FormulaC20H20BrN3O2S.2HCl
Solubility≥51.9mg/mL in DMSO
Chemical Name(E)-N-(2-((3-(4-bromophenyl)allyl)amino)ethyl)isoquinoline-5-sulfonamide dihydrochloride
SDFDownload SDF
Canonical SMILESO=S(C1=CC=CC2=C1C=CN=C2)(NCCNC/C=C/C3=CC=C(Br)C=C3)=O.Cl.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]:

PKA酶活性测定

在终体积为0.2mL,包含50mM Tris-HCl(pH 7.0),10mM乙酸镁,2mM EGTA,1μM cAMP或不含cAMP,3.3-20 μM [γ-32P] ATP(4×105cpm),0.5μg酶,100μg组蛋白H2B和各化合物的反应混合物中测定cAMP依赖性蛋白激酶活性。

细胞实验 [1]:

细胞系

PC12D细胞

溶解方法

该化合物在DMSO中的溶解度 > 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。

反应时间

30μM、1小时

应用

在PC12D细胞中,H-89(30μM)显著抑制cAMP依赖性组蛋白IIh的磷酸化活性并抑制Forskolin诱导的神经突生长。

动物实验 [2]:

动物模型

大鼠模型

剂量

20或200 mg/kg,皮下注射,每日两次,共2天

应用

H89引起蛋白质磷酸化的不同修饰,磷酸化中变化最大的是异质核核糖核蛋白(hnRNP),果糖-1,6-二磷酸酶,NSFL1辅因子p47,所有这些都具有与cAMP / PKA潜在的调节关系。

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:

1Chijiwa, T., Mishima, A., Hagiwara, M., Sano, M., Hayashi, K., Inoue, T., Naito, K., Toshioka, T. and Hidaka, H. (1990) Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. J Biol Chem. 265, 5267-5272

2Davis, M. A., Hinerfeld, D., Joseph, S., Hui, Y. H., Huang, N. H., Leszyk, J., Rutherford-Bethard, J. and Tam, S. W. (2006) Proteomic analysis of rat liver phosphoproteins after treatment with protein kinase inhibitor H89 (N-(2-[p-bromocinnamylamino-]ethyl)-5-isoquinolinesulfonamide). J Pharmacol Exp Ther. 318, 589-595

生物活性

Description H 89 2HCl is a potent inhibitor of PKA with a Ki value of 48 nM.
Targets PKA S6K1        
IC50 48 nM(Ki) 80 nM        

质量控制

化学结构

H 89 2HCl

相关生物数据

SGX-523

相关生物数据

SGX-523

相关生物数据

SGX-523