EX 527

DescriptionEX-527 (49843-98-3) is a selective SIRT1 inhibitor (IC50=98 nM). Does not inhibit other HDACs or SIRT family members. Increases p53 acetylation following DNA damage. Cell permeable.

UsesEX-527 has been used:in 1% dimethyl sulfoxide, 30%, polyethylene glycol-400 and 1% Tween 80 for treating C57BL/6 N mice to study its effect on intestinal morphological changes and crypt cell apoptosisas a an inhibitor of sirtuin 1, in treating human cancer lines MCF-7 (Michigan cancer foundation-7) and HCT116 (colon cancer cell line) incubated in Dulbecco′s modified Eagle′s medium, to study its effect on mitochondrial ATP (adenosine triphosphate) productionIntracerebroventricularly infused in rat model of epileptogenesis, to access kainic acid–induced status epilepticus stimulated sirtuin 1 activity

UsesA selective inhibitor of SIRT1 over SIRT2 and SIRT3

UsesEX-527 is a potent and selective sirtuin 1 (SIRT1) inhibitor (IC50 38 nM) identified from a high throughput screen. EX-527 is more selective (200-500-fold) for SIRT1 than for SIRT2 or SIRT3 and has been shown to be a potent SIRT6 inhibitor using H3K56 deacetylation site based substrate. EX-527 does not inhibit class I/II HDAC activity at concentrations up to 100uM. Enhances p53 acetylation in response to DNA damaging agents. EX-527 is racemic; the active isomer (EX-243) gives similar results and potency whereas the other isomer (designated EX-242) is inactive.

General DescriptionA cell-permeable indole compound that acts as a potent and highly selective inhibitor of SIRT1 (IC50 = 98 nM). It inhibits other sirtuin family deacetylases only at much higher concentrations (IC50 = 19.6 and 48.7 μM for SIRT2 and SIRT3, respectively) and shows no inhibitory effect against class I and II HDACs or NAD glycohydrolase even at concentrations as high as 100 μM. Shown to be orally bioavailable with a serum half-life of 136 minutes in mice in vivo.