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Go 6976

现货
Catalog No.
A8341
PKC α/PKC β1抑制剂
组合的产品项目
规格价格库存 数量
25mg
¥ 4,200.00
Ship with 10-15 days
5mg
¥ 1,400.00
Ship with 10-15 days

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Background

Go 6976 is a selective inhibitor of PKC with IC50 value of 20 nM [1] [2].

Protein kinase C (PKC) is a family of protein kinase enzymes and plays an important role in controlling the function of other proteins by the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins [1-3].

Go 6976 is a potent PKC inhibitor and has a more potent activity with the reported PKC inhibitor H-7. When tested with nRT cells, Go 6976 showed a marked decrease the baseline T-current amplitude nearly 40% at the dose of 10 μM by inhibiting Ca2+-dependent PKC pathway [3]. In T cell lines ACH-2 and U1 infected with HIV-1, Go 6976 treatment effectively blocked viral transcription induced by Bryostain 1 or tumor necrosis factor α which lead to the inhibition of intracellular viral protein synthesis and viral shedding and also blocked IL-6 mediated posttranscriptional inducetion of viral protein [2].

It is also reported that Go 6976 is a potent inhibitor to EGFR and FLT3with IC50 value ranges from 0.033 nM to 3.3 μM and 0.7 nM, respectively [4] [5].

References:
[1].  Gschwendt, M., et al., Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett, 1996. 392(2): p. 77-80.
[2].  Qatsha, K.A., et al., Go 6976, a selective inhibitor of protein kinase C, is a potent antagonist of human immunodeficiency virus 1 induction from latent/low-level-producing reservoir cells in vitro. Proc Natl Acad Sci U S A, 1993. 90(10): p. 4674-8.
[3].  Joksovic, P.M., et al., Mechanisms of inhibition of T-type calcium current in the reticular thalamic neurons by 1-octanol: implication of the protein kinase C pathway. Mol Pharmacol, 2010. 77(1): p. 87-94.
[4].  Taube, E., et al., A novel treatment strategy for EGFR mutant NSCLC with T790M-mediated acquired resistance. Int J Cancer, 2012. 131(4): p. 970-9.
[5].   Yoshida, A., et al., Go6976, a FLT3 kinase inhibitor, exerts potent cytotoxic activity against acute leukemia via inhibition of survivin and MCL-1. Biochem Pharmacol, 2014. 90(1): p. 16-24.

Chemical Properties

Physical AppearanceA crystalline solid
StorageDesiccate at -20°C
M.Wt378.43
Cas No.136194-77-9
FormulaC24H18N4O
SynonymsGo6976;Go-6976
SolubilitySoluble in DMSO
Chemical Name3-(13-methyl-5-oxo-6,7-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12(13H)-yl)propanenitrile
SDFDownload SDF
Canonical SMILESO=C1NCC2=C3C(N(CCC#N)C4=CC=CC=C34)=C5N(C)C6=CC=CC=C6C5=C21
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

细胞实验[1]:

细胞系

HEL细胞

溶解方法

在DMSO中的溶解度大于10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

4 h,1 μM

应用

Go 6976是一个选择性的蛋白激酶C(PKC)钙依赖性同功酶的抑制剂,在体外对JAK2具有直接有效的抑制作用。Go 6976也可以抑制表达TEL-JAK2融合蛋白的细胞中的信号转导、增殖和存活。使用Go 6976处理原发性急性髓性白血病细胞可减少STAT的磷酸化和组成型STAT活性。

动物实验[2]:

动物模型

6-8周龄的Balb/c小鼠

剂量

2.5 mg/kg,腹腔注射

应用

Go 6976显著抑制LPS诱导的蛋白激酶D激活,减轻LPS/D-GalN诱导的肝损伤,提高LPS/D-GalN给药小鼠的存活率。Go 6976也能够抑制小鼠肝中丝裂原活化蛋白激酶(MAPKs)的激活,减少肿瘤坏死因子ɑ(TNF-ɑ)的表达,减少细胞凋亡和髓过氧化物酶(MPO)的活性

注意事项

请测试所有化合物在室内的溶解度,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]. Grandage V L, Everington T, Linch D C, et al. Go 6976 is a potent inhibitor of the JAK 2 and FLT3 tyrosine kinases with significant activity in primary acute myeloid leukaemia cells[J]. British journal of haematology, 2006, 135(3): 303-316.

[2]. Duan G J, Zhu J, Xu C Y, et al. Protective effect of Go 6976, a PKD inhibitor, on LPS/d-GalN-induced acute liver injury in mice[J]. Inflammation research, 2011, 60(4): 357-366.

质量控制

质量控制和MSDS

批次:

化学结构

Go 6976