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Go 6983

现货
Catalog No.
A8343
pan-PKC(pan-蛋白激酶C)抑制剂。
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,000.00
现货
5mg
¥ 850.00
现货
10mg
¥ 1,350.00
现货

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Background

Go 6983 is a selective inhibitor of PKCα, PKCβ, PKCγ, PKCδ and PKCμ with IC50 value of 7 nM, 7 nM, 6 nM, 10 nM, and 20 mM, respectively [1].

Protein kinase C (PKC) serves as the receptor for tumor-promoting phorbol esters, which are potent activators of conventional (c) and novel (n) PKCs and has several isotypes: PKCα, PKCβ, PKCγ, PKCδ, PKCη and PKCμ. PKCη is reported progressively increased in MCF-10A (non-tumorigenic breast cancer cells) and promotes breast cancer cell survival [2, 3].

Go 6983 is a potent PKC inhibitor and has a different mechanism with the reported PKC inhibitor Ro-317549. When tested with MCF-7 and T47D cells, Go 6983 showed reversible effect on the down-regulation of PKCαand PKCδ induced by PKC activator PDBu, while decreased the expression of PKCη which up-regulated by PDBu. Further, Go 6983 treatment inhibited the MCF-7 cell survival by inhibiting the expression of PKCη [2]. In ARCcPE cells, PMA treatment promoted the EMT process by up-regulating the expression of PKCs(PKCα, PKCβand PKCγ) which could be significantly inhibited by Go6983 treatment through inhibiting PKCs expression at the dose of 200 nM and completely inhibited at the dose of 1000 nM [3].

In chromaffin cells isolated from female mice, Go 6983 treatment before AP-stimulus protocol reconciled the basal capcacitance values, decreased the capacitance and reduced calcium current density in a PKC dependent manner. To note, these phenomenons were more obvious in female mice compared with male mice [4].

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].  Pal, D., S.P. Outram, and A. Basu, Upregulation of PKCeta by PKCepsilon and PDK1 involves two distinct mechanisms and promotes breast cancer cell survival. Biochim Biophys Acta, 2013. 1830(8): p. 4040-5.
[3].  He, H., et al., Phorbol ester phorbol-12-myristate-13-acetate induces epithelial to mesenchymal transition in human prostate cancer ARCaPE cells. Prostate, 2010. 70(10): p. 1119-26.
[4].  Chan, S.A., J. Hill, and C. Smith, Reduced calcium current density in female versus male mouse adrenal chromaffin cells in situ. Cell Calcium, 2012. 52(3-4): p. 313-20.

文献引用

1. Lee E, Wang J, et al. "DNMT1 Regulates Epithelial-Mesenchymal Transition and Cancer Stem Cells, Which Promotes Prostate Cancer Metastasis."Neoplasia. 2016 Sep;18(9):553-66. PMID:27659015

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt442.51
Cas No.133053-19-7
FormulaC26H26N4O3
SynonymsGoe 6983;Go6983;Go-6983
Solubility≥22.15mg/mL in DMSO
Chemical Name3-[1-[3-(dimethylamino)propyl]-5-methoxyindol-3-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione
SDFDownload SDF
Canonical SMILESCN(C)CCCN1C=C(C2=C1C=CC(=C2)OC)C3=C(C(=O)NC3=O)C4=CNC5=CC=CC=C54
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]:

结合实验

在100 μL反应体系中进行磷酸化反应。上述体系包含缓冲液C(50 mM Tris-HC1,pH 7.5,10 mM β-巯基乙醇),4 mM MgCl2,10 μg PS,100 nM TPA,5 μL Sf158细胞提取物作为重组PKCμ来源,或Sf9细胞提取物作为其它重组PKC同工酶来源,10 μg Syntide 2作为底物,以及ATP (含1 μCi [γ-32P]ATP)。在某些实验中,除去PS和TPA,然后加入指定浓度的各种抑制剂。在30 °C下,将其孵育10分钟后,转移50 μL实验混合物到20-mm方片磷酸纤维素纸上,终止反应。然后用去离子水将纸洗涤3次,用丙酮洗涤2次。通过液体闪烁计数测定每张纸上的放射性。

细胞实验 [2]:

细胞系

ARCcPE细胞

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 °C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 °C可放置数月。

反应条件

200和1000 nM;48小时

实验结果

在ARCaPE细胞中,Go6983 (200 nM) 显著抑制由PMA诱导的PKC(PKCα,PKCβ和PKCγ)表达上调。此外,在1000 nM的剂量下,Go 6983具有完全抑制作用。

动物实验 [3]:

动物模型

携带B16BL6肿瘤的小鼠

给药剂量

22 μg/小鼠,静脉注射

实验结果

在小鼠B16BL6肺肿瘤模型中,Go 6983 (22.0 μg) 显着抑制肿瘤转移 (51.2%)。

其它注意事项

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]. 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]. He, H., et al., Phorbol ester phorbol-12-myristate-13-acetate induces epithelial to mesenchymal transition in human prostate cancer ARCaPE cells. Prostate, 2010. 70(10): p. 1119-26.

[3]. Kim HR, Lee KH, Park SJ, Kim SY, Yang YK, Tae J, Kim J. Anti-cancer activity and mechanistic features of a NK cell activating molecule. Cancer Immunol Immunother. 2009 Oct;58(10):1691-700.

生物活性

描述 Go-6983是pan-蛋白激酶C的抑制剂,作用于PKCα、PKCβ、PKCγ和PKCδ的IC50值分别为7 nM、7 nM、6 nM和10 nM。
靶点 PKCγ PKCα PKCβ PKCδ PKCζ PKCμ
IC50 6 nM 7 nM 7 nM 10 nM 60 nM 20 μM

质量控制

化学结构

Go 6983

相关生物数据

Go 6983