货号：E0146

储存条件：粉末-20°C可保存3年；液体-80°C可保存12月。

产品描述

SIRT1 is an enzyme which can remove acetyl groups without hydrolysis of NAD⁺ and can deacetylate p53 to modulate its function such as DNA damage-induced cell death. EX-527 is a novel, potent, and specific inhibitor of SIRT1 catalytic activity with IC50 value of 38nM (measure by activity of GST-tagged human SIRT1 purified from 293T cells), almost no activity to SIRT2 (IC50=19.6μM) or SIRT3 (IC50=48.7μM). Treatment with 1μM EX-527 for 6h after DNA damage by etoposide could enhance the level of p53 acetylation on K382 site in NCI-H460 cells. And this inhibition of SIRT1 catalytic activity by EX-527 could also be observed after treatment with adriamycin, hydroxyurea, or hydrogen peroxide in NCI-H460 cells, or in U-2 OS, MCF-7 and HMEC treated with etoposide. However, p53-controlled gene expression, such as p21, as well as cell survival or proliferation are not altered by inhibition of SIRT1 through EX-527 in these p53-positive cell lines. Inhibition of Sirt by EX-527 induced apoptosis-like changes in blood platelets, associated with a rise in active Bax and a significant drop in platelet count. Administration of 20mg/kg EX-527 led to a reduction in the number of reticulated platelets and thrombocytopenia in mice.

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