product name Go6976
Description: Go6976 is a potent PKC inhibitor with IC50 of 7.9 nM, 2.3 nM, and 6.2 nM for PKC (Rat brain), PKCα, and PKCβ1, respectively. 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.
References: J Biol Chem. 1993 May 5;268(13):9194-7; Br J Haematol. 2006 Nov;135(3):303-16.
377.42
Formula
C24H18N4O
CAS No.
136194-77-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 18 mg/mL (47.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% CMC Na+1% Tween 80: 30mg/mL
Synonyms
PD406976
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19421361
| In Vitro |
In vitro activity: Go6976 have no effect on the kinase activity of the Ca(2+)-independent PKC subtypes delta, epsilon, and zeta. Beside WT JAK2, Go6976 also inhibits the mutant forms (JAK2 V617F and TEL-JAK2) found in haematological malignancies, and has activity against mutant forms of FLT3. In AML cells, Go6976 reduces the survival to 55% of control in FLT3-ITD cases and to 69% in FLT3-WT samples. Go 6976 potently inhibits HIV-1 induction by Bryostatin 1, tumor necrosis factor alpha, and interleukin 6. Kinase Assay: In brief, for measuring PKCα, and PKCβ1 and PKC from rat brain, the assay mixture of 200 μl contains 50 mM HEPES (pH7.5), 5 mM MgCl2, 1 mM EDTA, 1.25 mM EGTA, 1.32 mM CaC12, 1 mM dithiothreitol, 1 μg of phosphatidylserine, 0.2 μg of diolein, 40 μg of histone Hi, 10 μM [γ-32P]ATP (1 μCi/ml), and 5-10 units (pmol of Pi/min) of PKC. Assays are started by the addition of [γ-32P]ATP, incubated for 5 min at 30 °C, stopped by the addition of 2 ml of 8.5% H3PO4, filtered through 0.45-μm nitrocellulose filters, and evaluated by scintillation counting. Cell Assay: Cells are suspended at 2 × 105 per point in 200 μl RPMI/10% FCS. The inhibitor under investigation is added at the appropriate concentration and the cells incubated for 48 h at 37°C, 5% CO2. MTS activity is measured by CellTiter kit according to the manufacturers instructions. Results are expressed as a percentage of control (cells without inhibitor). |
|---|---|
| In Vivo | Go6976 (2.5 mg/kg i.p.), as a PKD inhibitor, effectively prevents LPS/D: -GalN-induced acute liver injury by inhibition of MAPKs activation to reduce TNF-α production, and significantly improves the survival of LPS/D-GalN-challenged mice. |
| Animal model | LPS/D-GalN-challenged mice |
| Formulation & Dosage | Dissolved in DMSO; 2.5 mg/kg; i.p. injection |
| References | J Biol Chem. 1993 May 5;268(13):9194-7; Br J Haematol. 2006 Nov;135(3):303-16; Inflamm Res. 2011 Apr;60(4):357-66. |
