S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide

Description

The histone H3 lysine 27 (H3K27) methyltransferase EZH2 plays an important role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. GSK126 is a selective, S-adenosyl-methionine-competitive small molecule inhibitor of EZH2 methyltransferase activity (K_i = 0.57 nM; IC₅₀ = 9.9 nM versus that of EZH1: K_i = 89 nM; IC₅₀ = 680 nM). It is more than 1,000-fold selective for EZH2 over other histone methyltranferases, including both SET-domain-containing and non-SET-domain-containing methyltransferases. At concentrations of 7-252 nM, it has been shown to inhibit global H3K27 trimethylation levels and to reactivate silenced PRC2 target genes. Furthermore, GSK126 can inhibit the proliferation of EZH2 mutant DLBCL cell lines (IC₅₀ = 28-61 nM) as well as the growth of EZH2 mutant DLBCL xenografts in mice receiving a daily dose of 50 mg/kg.

The Uses of S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide

GSK126 is a potent and highly selective S-adenosyl-methionine-competitive small molecule inhibitor of EZH2 methyltransferase enzyme activity. The inhibition activity of GSK126 on EZH2 activity may pro vide a promising treatment for EZH2 mutant lymphoma.

The Uses of S)-1-(sec-butyl)-N-((4,6-diMethyl-2-oxo-1,2-dihydropyridin-3-yl)Methyl)-3-Methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxaMide

GSK126 is a potent and highly selective S-adenosyl-methionine-competitive small molecule inhibitor of EZH2 methyltransferase enzyme activity. The inhibition activity of GSK126 on EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.

Definition

ChEBI: 1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-methyl-6-[6-(1-piperazinyl)-3-pyridinyl]-4-indolecarboxamide is a member of piperazines and a member of pyridines.

Storage

Store at -20°C

References

1. sato, t., et al., prc2 overexpression and prc2-target gene repression relating to poorer prognosis in small cell lung cancer. sci rep, 2013. 3(1911). 2. mccabe, m.t., et al., ezh2 inhibition as a therapeutic strategy for lymphoma with ezh2-activating mutations. nature, 2012. 492(7427): p. 108-12. 3. van aller, g.s., et al., long residence time inhibition of ezh2 in activated polycomb repressive complex 2. acs chem biol, 2014. 9(3): p. 622-9. 4. yeh, c.m., et al., epigenetic silencing of arntl, a circadian gene and potential tumor suppressor in ovarian cancer. int j oncol, 2014. 45(5): p. 2101-7.