EX 527 (Selisistat)
Catalog No.S1541 Synonyms: SEN0014196
Molecular Weight(MW): 248.71
EX 527 (Selisistat) is a potent and selective SIRT1 inhibitor with IC50 of 38 nM in a cell-free assay, exhibits >200-fold selectivity against SIRT2 and SIRT3. Phase 2.
Cited by 12 Publications
4 Customer Reviews
The eect of Melatonin, luzindole, and EX527 treatment on apoptotic index, infarct size, lactate dehydrogenase (LDH) release, and CK release in IR-injured hearts. Representative photomicrographs of in situ detection of apoptotic myocytes by TUNEL staining. Green ﬂuorescence shows TUNEL-positive nuclei; blue ﬂuorescence shows nuclei of total cardiomyocytes; original magniﬁcation 9x400. Sacle bar: 100 um.
J Pineal Res 2014 57(2), 228-38. EX 527 (Selisistat) purchased from Selleck.
EX-527 decreases bone marrow atrophy signiﬁcantly in the lethal septic model (H & E; original magniﬁcation, x 40). Tissue samples of long bones (femur and tibia) were harvested at 48 hours after CLP. Samples were processed and stained with H & E, and representative images were chosen from different experimental groups. Semiquantitative pathology scores for bone marrow atrophy were graded according to the diameter proportion of veins to bone marrow cells (mean T SEM, n = 5-6 animals per group).
J Trauma Acute Care Surg 2014 10.1097/TA.0347. EX 527 (Selisistat) purchased from Selleck.
Western blot analysis of acetylated-lysine in Ex-527-treated embryos. Embryos were treated at the 2-cell stage with 100 and 200 umol/L of Ex-527, and extracts were collected 12 h later. Predictable band size of p53 is 53 kDa.
Dev Growth Differ 2014 56(6), 460-8. EX 527 (Selisistat) purchased from Selleck.
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|Description||EX 527 (Selisistat) is a potent and selective SIRT1 inhibitor with IC50 of 38 nM in a cell-free assay, exhibits >200-fold selectivity against SIRT2 and SIRT3. Phase 2.|
|Features||Greater potency, specificity, stability, and lower toxicity than other inhibitors of SIRT1 catalytic activity identified to date.|
EX 527 exhibits potently inhibitory effect against SIRT1 deacetylase activity in a concentration-dependent manner with an IC50 of 38 nM, displays much lower activity against SIRT2 and SIRT3 with IC50 values of 19.6 μM and 48.7 μM, respectively. EX 527 does not inhibit SIRT4-7 and class I/II HDAC activity at concentrations up to 100 μM. EX-527 alone (1 μM) has no detectable effect on the acetylation of p53 lysine 382 in NCI-H460 cells. EX-527 significantly increases the amount of acetylated p53 in NCI-H460 cells, human mammary epithelial cells, U-2 OS and MCF-7 cells subjected to genotoxic agents such as Etoposide, Doxorubicin, Hydroxyurea, and Hydrogen peroxide, which is more effective than that caused by Nicotinamide (5 mM). But surprisingly EX 527 does not result in detectable effects on p53-controled gene expression, cell survival, or cell proliferation.  EX 527 causes a 90% increase in cell number of HCT116 cells after 7 days in the condition of 0.1% serum but not 10% serum, suggesting that SIRT1 is a significant regulator of cell proliferation during growth factor deprivation conditions.  EX 527 abrogates resveratrol effects on glucose responses, and prevents resveratrol-induced up-regulation of Glut2, glucokinase, Pdx-1, and Tfam in INS-1E Cells, due to the opposite effect of EX 527 and resveratrol on SIRT1 deacetylase activity. 
|In vivo||Administration of EX 527 (~10 μg) to rats increases hypothalamic acetyl-p53 levels by inhibiting hypothalamic SIRT1 activity. Co-administration of EX 527 with ghrelin markedly blunts the orexigenic action of ghrelin by decreasing the pAMPK levels, increasing the ACC levels, and abolishing the higher expression of the transcription factors FoxO1, pCREB, and Bsx and the neuropeptides NPY and AgRP in the hypothalamic arcuate nucleus. |
Inhibition of GST-SIRT1 deacetylase activity:293T cells are transiently transfected with GST-tagged human SIRT1 in the pDEST27 Gateway vector using FuGENE-6. After 48 hours, the cells are lysed with 50 mM Tris, pH 8.0, 120 mM NaCl, 1 mM EDTA, and 0.5% Nonidet P-40, supplemented with Complete Mini protease inhibitor cocktail tablets. GST-SIRT1 is purified from lysates using glutathione-Sepharose beads and washed extensively in the above buffer. The deacetylation assay is performed with approximately 30 ng of GST-SIRT1 in the presence of EX 527 (48 pM to 100 μM). Deacetylation is measured using the Fluor de Lys kit using a fluorogenic peptide encompassing residues 379 to 382 of p53, acetylated on lysine 382. The acetylated lysine residue is coupled to an aminomethylcoumarin moiety. The peptide is deacetylated by SIRT1, followed by the addition of a proteolytic developer that releases the fluorescent aminomethylcoumarin. Briefly, enzyme preparations are incubated with 170 μM NAD+ and 100 μM p53 fluorogenic peptide for 45 minutes at 37 °C followed by incubation in developer for 15 minutes at 37 °C. Fluorescence is measured by excitation at 360 nm and emission at 460 nm and enzymatic activity is expressed in relative fluorescence units.
|In vitro||DMSO||50 mg/mL (201.03 mM)|
|Ethanol||18 mg/mL (72.37 mM)|
|In vivo||1% DMSO+30% polyethylene glycol+1% Tween 80||14 mg/mL|
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01485965||Completed||Huntingtons Disease||Siena Biotech S.p.A.||November 2011||Phase 1|
|NCT01521585||Completed||Huntingtons Disease||Siena Biotech S.p.A.||November 2011||Phase 2|
|NCT01485952||Completed||Huntington Disease||Siena Biotech S.p.A.|Seventh Framework Programme|European Huntingtons Disease Network||March 2011||Phase 1|
|NCT01521832||Completed||Huntingtons Disease||Siena Biotech S.p.A.||October 2009||Phase 1|
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