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Go 6976 (Synonyms: Go6976;Go-6976)

Catalog No.GC15564

Go 6769 est un inhibiteur de la protéine kinase C (PKC), avec une IC50 de 20 nM.

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Go 6976 Chemical Structure

Cas No.: 136194-77-9

Taille Prix Stock Qté
5mg
101,00 $US
En stock
25mg
303,00 $US
En stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment[1]:

Cell lines

HEL cells

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

4 h, 1 µM

Applications

Go 6976 is a selective inhibitor of the calcium-dependent isozymes of protein kinase C (PKC) and has a direct and potent inhibitory effect on JAK2 in vitro. Go 6976 also blocked signalling, proliferation and survival in cells expressing TEL-JAK2 fusion protein. In primary acute myeloid leukaemia cells, treatment with Go 6976 reduced STAT phosphorylation and constitutive STAT activity.

Animal experiment [2]:

Animal models

6-8 week-old Balb/c mice

Dosage form

2.5 mg/kg, i.p.

Application

Go 6976 significantly inhibited LPS-induced protein kinase D activation, relieved LPS/D-GalN-induced liver injury and improved the survival of LPS/D-GalN-administered mice. Go 6976 could also inhibit the activation of mitogen-activated protein kinases (MAPKs), reduce expression of tumor necrosis factor-a (TNF-ɑ), and decrease apoptosis and myeloperoxidase (MPO) activity in liver of mice.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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.

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

Cas No. 136194-77-9 SDF
Synonymes Go6976;Go-6976
Chemical Name 3-(13-methyl-5-oxo-6,7-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12(13H)-yl)propanenitrile
Canonical SMILES O=C1NCC2=C3C(N(CCC#N)C4=CC=CC=C34)=C5N(C)C6=CC=CC=C6C5=C21
Formula C24H18N4O M.Wt 378.43
Solubility DMF: 10 mg/ml,DMF:PBS (pH 7) (1:10): 0.1 mg/ml,DMSO: 10 mg/ml Storage Store at -20°C,protect from light
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.6425 mL 13.2125 mL 26.425 mL
5 mM 0.5285 mL 2.6425 mL 5.285 mL
10 mM 0.2642 mL 1.3212 mL 2.6425 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 15 reference(s) in Google Scholar.)

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