2. Epigenetics
  3. Histone Methyltransferase
  4. GSK126

GSK126 (GSK2816126A) est un puissant inhibiteur hautement sélectif de la EZH2 méthyltransférase avec un IC50 de 9,9 nM.

GSK126 (GSK2816126A) ist ein starker, hochselektiver Inhibitor der EZH2-Methyltransferase mit einem IC50-Wert von 9,9 nM.

GSK126 (GSK2816126A) is a potent, highly selective inhibitor of EZH2 methyltransferase with an IC50 of 9.9 nM.

For research use only. We do not sell to patients.

GSK126 Chemical Structure

GSK126 Chemical Structure

CAS No. : 1346574-57-9

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 83 In-stock
Solution
10 mM * 1 mL in DMSO USD 83 In-stock
Solid
1 mg USD 29 In-stock
5 mg USD 72 In-stock
10 mg USD 108 In-stock
50 mg USD 288 In-stock
100 mg USD 480 In-stock
200 mg USD 792 In-stock
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Customer Review

Based on 68 publication(s) in Google Scholar

GSK126 Related Antibodies

Top Publications Citing Use of Products

64 Publications Citing Use of MCE GSK126

WB

    GSK126 purchased from MedChemExpress. Usage Cited in: Cell. 2018 Sep 20;175(1):186-199.e19.  [Abstract]

    Cells are treated with EPZ-6438 (1 μM) or GSK126 (1 μM) for 6 days. Protein levels are analyzed by immunoblotting. Cells are treated with EPZ-6438 (1 μM), JQ1 (0.25 μM) alone or combination for 6 days. Protein levels are analyzed by immunoblotting.

    GSK126 purchased from MedChemExpress. Usage Cited in: J Exp Med. 2018 May 7;215(5):1365-1382.  [Abstract]

    Immunoblot analysis of Ezh2, H3K27me3, H3, and Hsp60 (loading control) in whole-cell lysates of the indicated proinflammatory genes of macrophages or microglia that are pretreated with DMSO or GSK126 (4 μM) for 3 d and then left nontreated (NT) or stimulated for 6 h with the ligands of different TLRs.

    GSK126 purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2018 Jan 26;9(2):129.  [Abstract]

    The effects of treatment with the indicated epigenetic inhibitors on cleaved PARP (Clv-PARP) expression in both PC9/ER and HCC827/ER cells. β-actin is used as a loading control.

    GSK126 purchased from MedChemExpress. Usage Cited in: Oncotarget. 2015 Sep 29;6(29):27023-36.  [Abstract]

    This includes ATF3 (Activating Transcription Factor 3) and metastasis suppressor NDRG1 (N-Myc Downstream Regulated Gene 1) that also shows an upregulation in protein expression (phosphorylated at threonine 346) with GSK126 in two EZH2 mutant cell lines by western blot.

    View All Histone Methyltransferase Isoform Specific Products:

    View All Isoforms
    EZH1 EZH2 DOT1L SMYD2 SMYD3 SUV39H2/KMT1B EHMT2/G9a/KMT1C EHMT1/GLP/KMT1D SETDB1/KMT2G SETD2/KMT3A NSD2/MMSET/WHSC1 SETD7/KMT7 SETD8/KMT5A PRMT1 PRMT3 PRMT4 PRMT5 PRMT6 PRMT7 PRMT8

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    GSK126 (GSK2816126A) is a potent, highly selective inhibitor of EZH2 methyltransferase with an IC50 of 9.9 nM[1].

    IC50 & Target[1]

    EZH2

    9.9 nM (IC50)

    In Vitro

    GSK126 potently inhibits both wild-type and mutant EZH2 methyltransferase activity with similar potencies (Ki=0.5-3 nM) independent of substrate used, and is competitive with S-adenosyl-methionine (SAM) and non-competitive with peptide substrates. GSK126 is highly selective against other methyltransferases and multiple other protein classes (EZH1, IC50=680 nM)[1]. Treatment of three SCLC cell lines with GSK126, induces growth inhibition. SCLC cell lines (Lu130, H209, and DMS53) are treated with 0.5, 2, and 8 μM GSK126, and growth curve is analyzed by WST-8 assay. Inhibition of cellular growth by GSK126 treatment is observed at 8 μM in all the three cell lines, while Lu130 and H209 are more sensitive to GSK126, even at lower doses[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    GSK126 Related Antibodies
    In Vivo

    GSK126 is administered intraperitoneally at a dose volume of 0.2 mL per 20 g body weight in female beige SCID mice. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice[1].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Molecular Weight

    526.67

    Formula

    C31H38N6O2
    CAS No.
    Appearance

    Solid

    Color

    White to yellow

    SMILES

    O=C(C1=CC(C2=CC=C(N3CCNCC3)N=C2)=CC4=C1C(C)=CN4[C@@H](C)CC)NCC5=C(C)C=C(C)NC5=O
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : 12.5 mg/mL (23.73 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.8987 mL 9.4936 mL 18.9872 mL
    5 mM 0.3797 mL 1.8987 mL 3.7974 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

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    Volume (start)

    V1

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    C2

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    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 1.25 mg/mL (2.37 mM); Clear solution

      This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: 1.25 mg/mL (2.37 mM); Suspended solution; Need ultrasonic

      This protocol yields a suspended solution of 1.25 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  50% PEG300    50% Saline

      Solubility: 10 mg/mL (18.99 mM); Suspended solution; Need ultrasonic

    • Protocol 2

      Add each solvent one by one:  20% SBE-β-CD in Saline adjusted to pH 4-4.5 with 1 N Acetic

      Solubility: 20 mg/mL (37.97 mM); Clear solution; Need ultrasonic and warming

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

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    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.98%

    COA (256 KB) HNMR (213 KB) RP-HPLC (148 KB) LCMS (122 KB)

    Handling Instructions (2659 KB)
    References
    Kinase Assay
    [1]

    The five-member PRC2 complex (Flag-EZH2, EED, SUZ12, AEBP2, RbAp48) containing either wild-type or mutant (A677G, Y641N, Y641C, Y641H, Y641S or Y641F) 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)[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Cell Assay
    [2]

    JUB- and PTRF-introduced DMS53 cells are seeded at density of 1×103 cells/well in 96-well plate, and cellular growth is analyzed using WST-8 kit at 12, 36, 60, and 84 h. Cellular growth of Lu130, H209, and DMS53 with treatment by DZNep or GSK126 is also analyzed using WST-8 kit. DZNep is dissolved in PBS at 5 mM, and cells are cultured at the final concentration of 5 μM. GSK126 is dissolved in DMSO at 10 mM, and cells are cultured at 0.5, 2, and 8 μM[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    Mice[1]
    GSK126 or vehicle is administered intraperitoneally at a dose volume of 0.2 mL per 20 g body weight. Pfeiffer or KARPAS-422 cells (1×107) in 100% Matrigel are implanted subcutaneously in female beige SCID mice. Tumors are measured with calipers, and block randomized according to tumour size into treatment groups. For efficacy studies, 10 mice are randomized in each treatment group before the initiation of dosing and GSK126 treatment is initiated once the tumour volumes are approximately 200 mm3 in the Pfeiffer and KARPAS-422 studies and 500 mm3 in the KARPAS-422 intermittent dosing study. Mice are weighed and tumors measured with calipers twice weekly. Two-tailed t-tests are conducted assuming two samples of equal variance.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.8987 mL 9.4936 mL 18.9872 mL 47.4681 mL
    5 mM 0.3797 mL 1.8987 mL 3.7974 mL 9.4936 mL
    10 mM 0.1899 mL 0.9494 mL 1.8987 mL 4.7468 mL
    15 mM 0.1266 mL 0.6329 mL 1.2658 mL 3.1645 mL
    20 mM 0.0949 mL 0.4747 mL 0.9494 mL 2.3734 mL
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    GSK126 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    GSK1261346574-57-9GSK2816126AGSK 126GSK-126Histone MethyltransferaseInhibitorinhibitorinhibit

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