product name Bisindolylmaleimide I
Description: GF109203X is a potent and highly selective PKC inhibitor with IC50 of 20 nM, 17 nM, 16 nM, and 20 nM for PKCα, PKCβI, PKCβII, and PKCγ in cell-free assays, respectively, it showed more than 3000-fold selectivity for PKC as compared to EGFR, PDGFR and insulin receptor. GF-109203X inhibited GSK-3 in vitro, when assayed either in cell lysates IC50 360 nM or in GSK-3beta immunoprecipitates IC50 170 nM derived from rat epididymal adipocytes.
References: J Biol Chem. 1991;266(24):15771-81; Br J Cancer. 1996;74(6):897-905; Br J Pharmacol. 2002;135(1):239-47.
412.48
Formula
C25H24N4O2
CAS No.
133052-90-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 82 mg/mL (198.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
GO 6850 , Bisindolylmaleimide I
other peoduct :
| In Vitro |
In vitro activity: GF109203X, as an ATP-competitive PKC inhibitor, prevents platelet aggregation induced by stimuli that activate PKC, and has the potential as a tool for studying the involvement of PKC in signal transduction pathways. GF 109203X produces reversal activity on P-glycoprotein and MRP -mediated multidrug resistance. PKC inhibition by GF109203X significantly reduces carbachol-stimulated ERK1/2 activation and the subsequent proliferation of SNU-407 colon cancer cells. Kinase Assay: Protein kinase C is arrayed by measuring 32PI transferred from [gamma-32PI] ATP to lysine-rich histone type Ill-s. The reaction mixture (80 μL) contained 50 mM Tris-HCI. pH 7.4, 100 μM CaCl2, 10 mM MgCI2, 37.5 μL/mL histone type Ill-s, 10 μM [gamma-32PI] ATP (1250 cpm/pmol), 31 μM bovine brain phosphatidylserine and 0.5 μM 1,2 sn-dioleylglycerol. Fifteen μL of purified PKC (final concentration in assay 0.38 μg/mL) is added to the incubation mixture. After 10 min at 30°C, the reaction is stopped by addition of 30 μL of casein 30 mg/mL and 0.9 ml of 12% trichloroacetic acid. The acid precipitable material is collected by centrifugation, dissolved in 1N NaOH (100μL) and precipitated again with 1 ml of 12% trichloroacetic acid. The pellet is dissolved in 1N NaOH (100μL) and 32P incorporation is measured by scintillation counting in Aquasol. Cell Assay: Cell proliferation is monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cells are seeded in 96-well plates and allowed to grow overnight. The cells are serum-starved for 18–24 hours and then treated with 1 mM carbachol for 48 hours in 100 μL serum-free RPMI 1640. Inhibitors are added 30 min prior to carbachol treatment. Following the treatment, 10 μL of MTT solution (5 mg/ml) is applied to each well, and the plates were incubated for 3 h at 37 °C. After the medium is removed, the formazan crystals formed are solubilized in 100 μL DMSO. The absorbance at 570 nm is measured using a microplate reader and the background absorbance at 690 nm is subtracted. Each assay is performed in triplicate. |
|---|---|
| In Vivo | GF109203X (10 μg/mouse, i.pl.) dose-dependently inhibits BK-induced mechanical allodynia in Wistar rats. |
| Animal model | Wistar rats |
| Formulation & Dosage | Dissolved in10% DMSO in saline; 10 μg; i.p. injection |
| References | J Biol Chem. 1991 Aug 25;266(24):15771-81; Br J Cancer. 1996 Sep;74(6):897-905; Br J Pharmacol. 2002 Jan;135(1):239-47. |
