S28448-5mg MDL-800 2275619-53-7 98% 5mg 640.00 现货

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商品详情

产品描述： SIRT6, responsible for deacetylation of histone H3 Nε-acetyl-lysines 9 (H3K9ac) and 56 (H3K56ac), is a tumor suppressor which has frequently been found to have low expression in various cancers. MDL-800 is a selective SIRT6 activator. It increased the deacetylase activity of SIRT6 by up to 22-fold and led to a global decrease in H3K9ac and H3K56ac levels in human hepatocellular carcinoma (HCC) cells. Also, it inhibited the proliferation of HCC cells via SIRT6-driven cell-cycle arrest and was effective in a tumor xenograft model.
体外研究： MDL‐800 (Figure1a) is a selective allosteric activator of SIRT6. It stimulates SIRT6 catalytic activity and promotes the binding affinities of substrate to SIRT6. It was therefore tested whether MDL‐800 treatment improved the quality of old murine (2‐year‐old)derived iPSCs. It was first validated that MDL‐800 enhances the enzymatic activity of mouse SIRT6. The iPSCs (induced pluripotent stem cells) derived from the old mice with MDL‐800 were pretreated at concentrations of 5 μM and 20 μM for 24 hr, and then analyzed the level of a SIRT6 substrate H3K56Ac. It was found that, consistent with previous reports on human SIRT6, treating the mouse iPSCs with MDL‐800 at 20 μM promoted the deacetylation of H3K56Ac (Figure1b), and prolonging the incubation time to 48 hr led to a further reduction in acetylation level of H3K56Ac (Figure1c). These data indicate that MDL‐800 might also directly activate the catalytic activity of mouse SIRT6. To further demonstrate that MDL‐800 affects the acetylation level of H3K56Ac through monitoring mouse SIRT6 activity, iPSCs derived from Sirt6 +/+ mouse embryonic fibroblasts (MEFs) or Sirt6 −/− MEFs were treated with MDL‐800. It was found that Sirt6 deficiency abrogated the MDL‐800 mediated promotion of H3K56Ac deacetylation (Figure S1a,b). Taken together, the results indicate that MDL‐800 specifically activates SIRT6 enzymatic activity in mouse iPSCs. Reference: Aging Cell. 2020 Aug; 19(8): e13185.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431819/
体内研究： The pluripotency and in vivo differentiation potential of mouse iPSCs were evaluated by chimera experiments. Old C57BL/6 murinederived iPSCs were first infected with lentivirus bearing vectors encoding GFP for labeling, and the GFP+ cells were sorted by FACS. GFP+ mouse iPSCs were pretreated with MDL‐800 before microinjection into blastocysts. Then, the embryos were transplanted into the uteruses of pseudo‐pregnant ICR mice. Strikingly, it was found that embryos generated from mouse iPSCs treated with MDL‐800 showed a stronger green fluorescence, indicating a higher capacity to differentiate into three lineages in chimeric mice (Figure2b). In addition, the skins of embryos were dissociated into single cells and assessed by FACS for quantitative analysis. The result clearly showed that the percentage of GFP+ cells were approximately 3‐fold higher in MDL‐800 treated group than in the control group (Figure2c), indicating an improvement in in vivo differentiation of the same cell line upon MDL‐800 treatment. Further evidence from agouti coat color of the adult mice gave a similar result. There was a remarkable increase in the percentage of mice with a chimeric black coat color in the MDL‐800 treated group as compared to control group (Figure 2d,e). Reference: Aging Cell. 2020 Aug; 19(8): e13185.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431819/
保存条件： -20℃
配置溶液浓度参考：

	1mg	5mg	10mg
1 mM	1.597 ml	7.983 ml	15.967 ml
5 mM	0.319 ml	1.597 ml	3.193 ml
10 mM	0.16 ml	0.798 ml	1.597 ml
50 mM	0.032 ml	0.16 ml	0.319 ml

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