| Identification | Back Directory | [Name]
N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamide | [CAS]
1346572-63-1 | [Synonyms]
GSK03
GSK503
CS-1698
GSK-503;GSK 503
GSK-503;GSK503;GSK 503
GSK-503,EZH2 inhibitor
N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamide
N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-indole-4-carboxamide
1H-Indole-4-carboxamide, N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]- | [Molecular Formula]
C31H38N6O2 | [MDL Number]
MFCD28405142 | [MOL File]
1346572-63-1.mol | [Molecular Weight]
526.67 |
| Chemical Properties | Back Directory | [Boiling point ]
798.6±60.0 °C(Predicted) | [density ]
1.24±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≥21.65 mg/mL in DMSO; insoluble in H2O; ≥26.85 mg/mL in EtOH with gentle warming | [form ]
solid | [pka]
11.93±0.10(Predicted) | [color ]
White to gray |
| Hazard Information | Back Directory | [Uses]
GSK503 is an EZH2 inhibitor for treating cancer. | [Biological Activity]
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]. | [in vivo]
In a melanoma mouse model, conditional EZH2 ablation as much as treatment with the GSK503 stabilizes the disease through inhibition of growth and virtually abolishes metastases formation without affecting normal melanocyte biology[2]. GSK503 displays favorable pharmacokinetics in mice. GSK503, but not vehicle, prevents the formation of germinal center after SRBC or NP-KLH immunization, phenocopying the Ezh2 null phenotype. GSK503 treatment leads to reduced numbers of GC B-cells by flow cytometry, reduces number and volume of GCs by immunohistochemistry, and impairs formation high affinity antibodies[1]. | [IC 50]
EZH2 | [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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| Company Name: |
D&C Chemicals
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| Telephone: |
+86-21-58447131 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList16963/0_EN.htm |
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