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Formula | C13H13ClN2O |
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Molecular Weight | 248.71 | CAS No. | 49843-98-3 | ||||
Solubility (25°C)* | In vitro | DMSO | 49 mg/mL (197.01 mM) | ||||
Ethanol | 49 mg/mL (197.01 mM) | ||||||
Water | Insoluble | ||||||
In vivo (Add solvents to the product individually and in order) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | Selisistat (EX 527, SEN0014196) 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. | ||
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In vitro | 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 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. [1] 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. [2] 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. [3] |
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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. [4] |
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Features | Greater potency, specificity, stability, and lower toxicity than other inhibitors of SIRT1 catalytic activity identified to date. |
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Data from [Data independently produced by J Pineal Res, 2014, 57(2), 228-38]
Data from [Cancer Res, 2014, 74(1), 298-308]
Data from [Data independently produced by J Trauma Acute Care Surg, 2014, 10.1097/TA.0347]
Data from [Data independently produced by Dev Growth Differ, 2014, 56(6), 460-8]
Genetic determinants of micronucleus formation in vivo [ Nature, 2024, 627(8002):130-136] | PubMed: 38355793 |
Genetic determinants of micronucleus formation in vivo [ Nature, 2024, 10.1038/s41586-023-07009-0] | PubMed: 38355793 |
Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics [ Sci Immunol, 2024, 9(93):eadj7238] | PubMed: 38489349 |
SIRT1 maintains bone homeostasis by regulating osteoblast glycolysis through GOT1 [ Cell Mol Life Sci, 2024, 81(1):204] | PubMed: 38700532 |
Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis [ Antioxidants (Basel), 2024, 13(4)424] | PubMed: 38671872 |
The mechanism by which SIRT1 regulates autophagy and EMT in drug-resistant oesophageal cancer cells [ Life Sci, 2024, 343:122530] | PubMed: 38401628 |
Mesenchymal stromal cells ameliorate mitochondrial dysfunction in α cells and hyperglucagonemia in type 2 diabetes via SIRT1/FoxO3a signaling [ Stem Cells Transl Med, 2024, szae038] | PubMed: 38864709 |
Effects of Melatonin and 3,5,3'-Triiodothyronine on the Development of Rat Granulosa Cells [ Nutrients, 2024, 16(18)3085] | PubMed: 39339685 |
Acetylation-induced proteasomal degradation of the activated glucocorticoid receptor limits hormonal signaling [ iScience, 2024, 27(2):108943] | PubMed: 38333702 |
α-Ketoglutarate improves cardiac insufficiency through NAD+-SIRT1 signaling-mediated mitophagy and ferroptosis in pressure overload-induced mice [ Mol Med, 2024, 30(1):15] | PubMed: 38254035 |
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