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GSK503

In stock
Catalog No.
B5833
EZH2 inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$150.00
In stock
5mg
$90.00
In stock
10mg
$140.00
In stock
50mg
$450.00
In stock

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GSK503 is a potent inhibitor of EZH2.

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme that catalyses trimethylation of lysine 27 in histone 3 (H3K27me3), and then induces chromatin compaction and consequently inhibits target genes transcription.

GSK503 is a potent EZH2 inhibitor with anticancer activity. In human melanoma cells, GSK503 significantly reduced H3K27me3 levels, induced G1 cell cycle arrest and slowed down cell growth [1].

In mice, GSK503 induced reversible weight loss by ~10%. In mice with skin melanomas, GSK503 reduced H3K27me3 levels in tumour and stromal cells, and significantly reduced the emergence of new skin melanomas. Also, GSK503 significantly inhibited the proliferation of tumour cells. In C57Bl/6 mice xenografted murine B16-F10 melanoma cells, GSK503 significantly reduced H3K27me3 levels and inhibited tumor growth. Also, GSK503 inhibited lymph node and lung metastases of melanoma and reduced lung nodule counts. GSK503 increased the expression of deoxycytidine kinase (DCK), adenosylmethionine decarboxylase 1 (AMD1) and WD repeat domain 19 (WDR19), which were EZH2 target genes [1].

Reference:
[1].  Zingg D, Debbache J, Schaefer SM, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun, 2015, 6: 6051.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt526.67
Cas No.1346572-63-1
FormulaC31H38N6O2
Solubility≥21.65 mg/mL in DMSO, <2.7 mg/mL in H2O, ≥26.85 mg/mL in EtOH with gentle warming
Chemical Name(Z)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-indole-4-carbimidic acid
SDFDownload SDF
Canonical SMILESCC(N(C1=CC(C2=CN=C(N3CCN(CC3)C)C=C2)=CC(/C(O)=N/CC4=C(O)N=C(C=C4C)C)=C51)C=C5C)C
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

Human melanoma cells

Preparation method

The solubility of this compound in DMSO is >21.65mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1 μM; 8 days; 37 ℃

Applications

GSK503 significantly reduced H3K27me3 levels, induced G1 cell cycle arrest and slowed down cell growth.

Animal experiment [1]:

Animal models

Mice engrafted subcutaneously with melanoma cells, C57Bl/6 mice xenografted murine B16-F10 melanoma cells

Dosage form

Intraperitoneal injections; 150 mg/kg; 35 consecutive days

Application

GSK503 treatment drastically reduced the emergence of new skin melanomas over time after treatment start. GSK503 treatment prevented murine melanoma growth. GSK503 significantly inhibited the proliferation of tumour cells. In C57Bl/6 mice xenografted murine B16-F10 melanoma cells, GSK503 significantly reduced H3K27me3 levels and inhibited tumor growth. GSK503 inhibited lymph node and lung metastases of melanoma and reduced lung nodule counts.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Zingg D, Debbache J, Schaefer SM, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun, 2015, 6: 6051.

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