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UNC0638 is a potent, selective and cell permeable G9a and GLP inhibitor, with a toxicity/function ratio of >100, compared to <6 for BIX01294. UNC0638 inhibits G9a HMTase with an IC₅₀?~15 nM and GLP, a closely-related H3K9 HMTase, with an IC₅₀~19 nM, but is more than 10,000-fold selective over other epigenetic targets. G9a (EHMT2) and GLP (EHMT1) catalyze the mono and dimethylation of lysine 9 of histone 3 (H3K9) and other non-histone substrates such as p53 and WIZ. UNC0638 treatment in a variety of cell lines resulted in lower global H3K9me2 levels, equivalent to levels observed in small hairpin RNA knockdown of G9a and GLP. UNC0638 inhibits H3K9 dimethylation in MDA-MB231 cells with an IC₅₀?of 81 nM. In mouse embryonic stem cells, UNC0638 reactivated G9a-silenced genes and a retroviral reporter gene in a concentration-dependent manner without promoting differentiation.

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How to Use:

• ?In vitro:??UNC0638 was used at 0.5μM in vitro and cellular assays.
• ?In vivo:?n/a

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Reference:

• 1. Vedadi M, et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. (2011) Nat Chem Biol. 7(8):566-74.
• 2. Kubicek S. et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. (2007) Mol. Cell 25, 473–481.
• 3. Shi Y, et al. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. (2008) Cell Stem Cell. 3(5):568-74

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