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H-89 2HCl

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Chemical Structure| 130964-39-5 同义名 : H-89 (hydrochloride);Protein Kinase Inhibitor H-89;5-Isoquinolinesulfonamide;H-89 dihydrochloride
CAS号 : 130964-39-5
货号 : A171227
分子式 : C20H22BrCl2N3O2S
纯度 : 99%+
分子量 : 519.283
MDL号 : MFCD00214120
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(202.2 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 5 mg/mL(9.63 mM)，配合低频超声，并水浴加热至45℃助溶
动物实验配方：
生物活性
靶点

  • PKA

    PKA, Ki:48 nM
描述 PKA is a ubiquitous cellular kinase, also known as cAMP-dependent protein kinase, and it is well-established that plays an important role in regulating several functions of cell processes, including regulation of glycogen, sugar, and lipid metabolism[1]. H-89 2HCl, as a newly synthesized isoquinolinesulfonamide, is a ATP-competitive, potent inhibitor of protein kinase A (PKA)(IC50 = 48 nM), and has weak inhibition on several other kinases with IC50 of 80, 120, 135, 270, 2600 and 2800 nM for S6K1, MSK1, PKA, ROCKII, PKBα and MAPKAP-K1b, respectively[2]. H-89 2HCl has since been used extensively for evaluation of the role of PKA in the heart, osteoblasts, hepatocytes, smooth muscle cells, neuronal tissue, epithelial cells, etc[3]. PC12D cells pretreatment with H-89 2HCl led to a dose-dependent inhibition of the forskolin-induced neurite outgrowth and protein phosphorylation. In vivo experimental method, in skinned EDL fibres of the rat, H-89 2HCl with 1-2 μM significantly slowed the repriming rate in rat skinned fibres. Moreover, rat brain ventricles following an injection with the PKA antagonist, H-89 2HCl, the body temperature is increased further due to the inhibition of TRPV1 phosphorylation[4].
作用机制 H-89 2HCl inhibit the significant modulator role of the cAMP-PKA intracellular signaling pathway mainly acting as a selective and potent inhibitor of protein kinase A (PKA).
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
CHO 10 μM Growth Inhibition Assay 1 h inhibits 5-HT induced cAMP production decrease 12569069
SK-N-MC 30 μM Function Assay 24 h reduces the down-regulation of β1-AR by isoproterenol by 50%  11705454
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.63mL

1.93mL

0.96mL

19.26mL

3.85mL

1.93mL
参考文献

[1]Dolan S, Nolan AM. Biphasic modulation of nociceptive processing by the cyclic AMP-protein kinase A signalling pathway in sheep spinal cord. Neurosci Lett. 2001;309(3):157-60.

[2]Chijiwa T, Mishima A, 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 Biol Chem. 1990;265(9):5267-72.

[3]Lochner A, Moolman JA. The many faces of H89: a review. Cardiovasc Drug Rev. 2006;24(3-4):261-74.

[4]Bao D, Zhao W, et al. H89 dihydrochloride hydrate and calphostin C lower the body temperature through TRPV1. Mol Med Rep. 2018;17(1):1599-1608.

[5]Seyedi SY, Salehi F, et al. Dual effect of cAMP agonist on ameliorative function of PKA inhibitor in morphine-dependent mice. Fundam Clin Pharmacol. 2014 Aug;28(4):445-54.

[6]Davis MA, Hinerfeld D, et al. Proteomic analysis of rat liver phosphoproteins after treatment with protein kinase inhibitor H89 (N-(2-[p-bromocinnamylamino-]ethyl)-5-isoquinolinesulfonamide). J Pharmacol Exp Ther. 2006 Aug;318(2):589-95. Epub 2006 May 10.