1346572-63-1

Basic information

• Product 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
• Synonyms: 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;GSK503;GSK03;GSK-503,EZH2 inhibitor;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
• CAS NO: 1346572-63-1
• Molecular Formula: C31H38N6O2
• Molecular Weight: 526.67242
• EINECS: -0
• Product Categories: API;Inhibitors
• Mol File: 1346572-63-1.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 798.6±60.0 °C(Predicted)
• Appearance: /
• Density: 1.24±0.1 g/cm3(Predicted)
• Solubility: ≥21.65 mg/mL in DMSO; insoluble in H2O; ≥26.85 mg/mL in EtOH with gentle warming
• PKA: 11.93±0.10(Predicted)
• CAS DataBase Reference: 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 DataBase Reference)
• NIST Chemistry Reference: 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(1346572-63-1)
• EPA Substance Registry System: 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(1346572-63-1)

Safety Data

• Hazardous Substances Data: 1346572-63-1(Hazardous Substances Data)

Usage

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].

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.

Upstream product

• 918524-63-7 1-methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine 
• 1346573-22-5 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxamide 

Relevant articles and documents

METHOD OF TREATMENT

The present invention relates to a method of treating T cell mediated inflammatory immune diseases or T cell mediated hypersensitivity diseases, which comprises administering to a human in need thereof an effective amount of a compound which inhibits EZH2 and/or EZH1, or a pharmaceutically acceptable salt thereof.