GSK126

Catalog No.S7061

GSK126 Chemical Structure

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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4 Customer Reviews

  • 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

Biological Activity

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.
Targets
EZH2 [1]
(Cell-free assay)
9.9 nM
In vitro

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. [1] In A687V EZH2-mutant cells, GSK126 treatment results in a global decrease in H3K27me3, robust gene activation, caspase activation, and decreased proliferation. [2] 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. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human Pfeiffer cells NFTTXWREgXSxdH;4bYPDqGG|c3H5 MVS3NkBp M13pdWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHBn\WmoZnXyJINmdGy|IHX4dJJme3OrbnegSXpJOiCDNk[3S{BufXSjboSgZZN{\XO|ZXSgZZMh\3Kxd4ToJIlvcGmkaYTpc44h[W[2ZYKgO|IhcHK|IHL5JHdUXC1zIHHzd4F6NCCJSUWwQVAvOThizszNMi=> NYrwb29yOjR5Nke4OVA>
human HeLa cells NVO3dFJxTnWwY4Tpc44h[XO|YYm= NFX6PYU4OiCq MmnwTY5pcWKrdHnvckBw\iCHWliyJIlvKGi3bXHuJGhmVGFiY3XscJMh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJGg{UzJ5bXWzJIxmfmWuczDpcoN2[mG2ZXSg[o9zKDd{IHjyd{BjgSCHTFnTRUBu\XSqb3SsJGlEPTB;MD6yPEDPxE1w M{\5d|I3OTh7MEe4
human U2932 cells MlfSR5l1d3SxeHnjxsBie3OjeR?= NWfGc|U5PzJiaB?= M3fBfWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHUzQTN{IHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCZU2StNUBie3OjeTygS2k2OD14Lkeg{txONg>? NWPp[VFGOjR5Nke4OVA>
human PC3 cells NWK0PJl2S3m2b4TvfIlkyqCjc4PhfS=> NYHX[ZBQPzJiaB?= NGHhSmpEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBRSzNiY3XscJMh[XO|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KFeVVD2xJIF{e2G7LDDHTVUxRTlwNDFOwG0v NHzTVogzPDd4N{i1NC=>
human Daudi cells M{D5VmN6fG:2b4jpZ:Kh[XO|YYm= MoW5O|IhcA>? M4ezc2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGRifWSrIHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCZU2StNUBie3OjeTygS2k2OD1zMT6yJO69VS5? MnrDNlQ4Pjd6NUC=
human T98G cells M4nWOWN6fG:2b4jpZ:Kh[XO|YYm= MVm3NkBp MkLzR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gWFk5TyClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkA4OiCqcoOgZpkhX1OWLUGgZZN{[XluIFfJOVA:OTJwNjFOwG0v MVqyOFc3Pzh3MB?=
human A549 cells Mn2wR5l1d3SxeHnjxsBie3OjeR?= MVS3NkBp NF3GZmlEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCPTR7IHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCZU2StNUBie3OjeTygS2k2OD1zOD63JO69VS5? NVjNSmJpOjR5Nke4OVA>
human U87MG cells NFTnV2JEgXSxdH;4bYPDqGG|c3H5 MXO3NkBp M4jPW2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHU5P02JIHPlcIx{KGG|c3Xzd4VlKGG|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCZU2StNUBie3OjeTygS2k2OD1{OD61JO69VS5? NYrwcnJwOjR5Nke4OVA>

... Click to View More Cell Line Experimental Data

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. [1]

Protocol

Kinase Assay:[1]
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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.
Cell Research:[1]
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  • Cell lines: 46 lymphoma cell lines
  • Concentrations: ~100 μM
  • Incubation Time: 6 days
  • Method: The optimal cell seeding is determined empirically for all cell lines by examining the growth of a wide range of seeding densities in a 384-well format to identify conditions that permitted proliferation for 6 days. Cells are then plated at the optimal seeding density 24 h before treatment (in duplicate) with a 20-point two fold dilution series of GSK126 or 0.15% DMSO. Plates are incubated for 6 days at 37°C in 5% CO2. Cells are then lysed with CellTiter-Glo (CTG) and chemiluminescent signal is detected with a TECAN Safire2 microplate reader. In addition, an untreated plate of cells is harvested at the time of compound addition (T0) to quantify the starting number of cells. CTG values obtained after the 6 day treatment are expressed as a percent of the T0 value and plotted against compound concentration. Data are fit with a four-parameter equation to generate a concentration response curve and the concentration of GSK126 required to inhibit 50% of growth (growth IC50) is determined.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Female beige SCID mice bearing Pfeiffer or KARPAS-422 tumors
  • Formulation: 20% captisol
  • Dosages: 150 mg/kg/day
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 3 mg/mL warmed (5.69 mM)
Water Insoluble
Ethanol Insoluble warmed
In vivo Add solvents to the product individually and in order:
4% DMSO+corn oil
0.5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 526.67
Formula

C31H38N6O2

CAS No. 1346574-57-9
Storage powder
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

  • Question 1:

    Does this drug require an activation step to be functional? For example, an acidic or basic environment.

  • Answer:

    GSK126 does not require an activation step to be functional.

Related Antibodies

Histone Methyltransferase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID