Molecular Weight(MW): 526.67
GSK126 is a potent, highly selective EZH2 methyltransferase inhibitor with IC50 of 9.9 nM, >1000-fold selective for EZH2 over 20 other human methyltransferases.
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HeLa cells were transfected with NS (nonspecific) or EZH2-specific siRNA for 48 h with protease inhibitors (10 μM E64 and 10 μM pepstatin-A). Cells were stained with LC3B antibody (green) and DAPI, and observed under confocal microscopy for LC3B puncta. Scale bars: 10 μm
Autophagy, 2015, 11(12):2309-22.. GSK126 purchased from Selleck.
Concentration-dependent cytotoxic effect of candidate therapeutics. a. KMBC (blue circles) and HuCCT1 (purple squares) cells and b: haploid BAP1 knockout (HAP1 BAP1 KO) (green circles) or parental haploid HAP1 cells (WT) (orange squares) were plated in 384-well plates (1,000 cells/well), and incubated with varying concentrations of the indicated drug. Cell viability was assessed after 72 h using Cell Titer GloR 2.0 assay. Data represents the average percent cell viability plotted against concentration of drug in nM from 4 replicates for each condition. The table indicates the inhibitory concentration at 50% effect (IC50) values for each drug for each of the cell lines
Mol Cancer, 2017, 16(1):22. GSK126 purchased from Selleck.
(C) Four GCBDLBCL cells lines [1 wild-type (wt), 3 mutated (mut) EZH2] were treated with 500 nmol/l BAY 1238097 or with an EZH2 inhibitor (DZNep and GSK126, both used at the concentration of 500 nmol/l) as single agents and in combination for 72 h. The arrow indicates the EZH2 correct band. Dimethyl sulphoxide (DMSO) alone was added as negative control cells. Membranes were hybridized with antibodies against EZH2, H3K27me3, histone H3 and GAPDH.
Br J Haematol, 2017. GSK126 purchased from Selleck.
Immunohistological analysis of H3K27me3 marks in Men1WT MEFs following 72 h stimulation using 10 μM of GSK343 or 3 μM of GSK126. Representative pictures of a H3K27me3 immunofluorescent staining counterstained with DAPI are shown. Graph shows the % of cells that retain a H3K27me3 staining following treatments.
Biochim Biophys Acta, 2017, 1860(4):427-437. GSK126 purchased from Selleck.
Purity & Quality Control
Choose Selective Histone Methyltransferase Inhibitors
|Description||GSK126 is a potent, highly selective EZH2 methyltransferase inhibitor with IC50 of 9.9 nM, >1000-fold selective for EZH2 over 20 other human methyltransferases.|
In vitro, GSK126 most potently inhibits H3K27me3, followed by H3K27me2 in both EZH2 wild-type and mutant DLBCL cell lines. GSK126 also effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines, and induces transcriptional activation of EZH2 target genes in sensitive cell lines.  In A687V EZH2-mutant cells, GSK126 treatment results in a global decrease in H3K27me3, robust gene activation, caspase activation, and decreased proliferation.  In parental H2087 cells, GSK126 inhibits the expression of VEGF-A and phosphorylated Ser(473)-AKT, and thus causes the inhibition of cell proliferation, migration and metastasis. 
|In vivo||In mice bearing KARPAS-422 and Pfeiffer xenografts, GSK126 (150 mg/kg/d, i.p.) decreases global H3K27me3, increases gene expression, and thus causes marked tumour regression. |
EZH2 assay:The five-member PRC2 complex (Flag–EZH2, EED, SUZ12, AEBP2, RbAp48) containing either wild-type or mutant EZH2 is prepared. GSK126 is dissolved in DMSO and tested at concentrations of 0.6 nM to 300 nM with a final DMSO concentration of 2.5%. In contrast to wild-type EZH2 which prefers H3K27me0 as a substrate in vitro, EZH2 Y641 mutants prefer H3K27me2 and have little activity with H3K27me0 or H3K27me1. The A677G mutant is distinct from both the wild-type and Y641 mutant forms of EZH2 in that it efficiently methylates H3K27me0, H3K27me1, and H3K27me2; therefore, histone H3 peptides (residues 21–44; 10 μM final) with either K27me0 (wild type, A677G EZH2), K27me1 (A677G EZH2), or K27me2 (A677G, Y641N, Y641C, Y641H, Y641S and Y641F EZH2) are used as methyltransferase substrates. GSK126 is added to plates followed by addition of 6 nM EZH2 complex and peptide. As the potency of GSK126 is at or near the tight binding limit of an assay run at [SAM] = Km, IC50 values are measured at a high concentration of the competitive substrate SAM relative to its Km (7.5 μM SAM where the SAM Km is 0.3 μM). Under these conditions, the contribution from the enzyme concentration becomes relatively small and accurate estimates of Ki can be calculated. Reactions are initiated with [3H]-SAM, incubated for 30 min, quenched with the addition of 500-fold excess unlabelled SAM, and the methylated product peptide is captured on phosphocellulose filters according to the vendor supplied protocol for MSPH Multiscreen plates. Plates are read on a TopCount after adding 20 μL of Microscint-20 cocktail. Apparent Ki values are calculated using the Cheng–Prusoff relationship for a competitive inhibitor. IC50=Ki (1+[S]/Km)+[E]/2, where E is the enzyme and S is the substrate.
|In vitro||DMSO||3 mg/mL warmed (5.69 mM)|
|In vivo||Add solvents individually and in order:
4% DMSO+corn oil
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Frequently Asked Questions
Does this drug require an activation step to be functional? For example, an acidic or basic environment.
GSK126 does not require an activation step to be functional.