Selisistat (EX 527) is a potent and selective inhibitor of the SIRT1 class III histone deacetylase enzyme. EX 527 has been used a powerful tool for studying the relationship between SIRT1 and cell regulation. The deacetylation of cortactin, a protein responsible for rearrangements of the actin cytoskeleton, is associated with cell motility and possibly tumorigenesis, and blocking of this deacetylation by EX 527 correlated to a decrease in cell motility. Blocking of SIRT1 by EX 527 also demonstrated that deacetylation of the important tumor suppressor protein p53 is mediated by SIRT1 as well.
Int J Biol Sci. 2022 Jan 31;18(4):1594-1611.
Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway
Selisistat (EX 527) purchased from AbMole
Int Immunopharmacol. 2022 Feb;103:108456.
Differential regulation of lipopolysaccharide-induced IL-1β and TNF-α production in macrophages by palmitate via modulating TLR4 downstream signaling
Selisistat (EX 527) purchased from AbMole
Int J Biochem Cell Biol. 2022 Aug;149:106246.
Adipose improves muscular atrophy caused by Sirtuin1 deficiency by promoting mitochondria synthesis
Selisistat (EX 527) purchased from AbMole
Free Radic Biol Med. 2018 Oct 17.
Resveratrol protects photoreceptors by blocking caspase- and PARP-dependent cell death pathways.
Selisistat (EX 527) purchased from AbMole
Mol Neurobiol. 2018 Apr;55(4):3067-3078.
17β-Estradiol via SIRT1/Acetyl-p53/NF-kB Signaling Pathway Rescued Postnatal Rat Brain Against Acute Ethanol Intoxication
Selisistat (EX 527) purchased from AbMole
 |
Source | Free Radical Biology and Medicine (2018). Figure 4. Ex-527 (Abmole Bioscience, Houston, TX, USA) |
| Method | western blot | |
| Cell Lines | 661W cells | |
| Concentrations | 180 μM | |
| Incubation Time | ||
| Results | As shown in Figure 4A–D, there is a lower cell death rate in the presence of RSV in both the GD and the light exposure groups compared to the control group, whereas treatment with Ex-527 reversed this trend (P < 0.01). |
 |
Source | Proc Natl Acad Sci U S A (2013). Figure 3. EX 527 |
| Method | Continuous Deacetylation Assay | |
| Cell Lines | Sir2Tm crystals | |
| Concentrations | 1 mM | |
| Incubation Time | 80 min | |
| Results | Ex-527 showed negligible affinities (Sir2Tm: Kd > 180 μM; Sirt3 Kd > 330 μM) to apo-enzymes and to the Sirtuins saturated with 1 mM peptide substrate (Sir2Tm: Kd > 170 μM; Sirt3: Kd > 180 μM). |
 |
Source | Proc Natl Acad Sci U S A (2013). Figure 1. EX 527 |
| Method | Activity assay | |
| Cell Lines | Sir2Tm crystals | |
| Concentrations | 1.5 mM | |
| Incubation Time | 80 min | |
| Results | Activity assays in presence of varying Ex-527 concentrations showed that inhibition of Sir2Tm and Sirt3 by Ex-527 is noncompetitive with substrate peptide (Fig. 1 E and F; Fig. S1A; Sir2Tm Ki = 1.8 ± 0.4 μM, Sirt3 Ki = 33.4 ± 4.4 μM). |
| Cell Experiment | |
|---|---|
| Cell lines | NCI-H460 cells, MCF-7 cells, U-2 OS cells, or HMEC cell lines |
| Preparation method | Cell viability assay. NCI-H460 cells, MCF-7 cells, U-2 OS cells, or HMEC were plated at 2,000 cells per well in opaque-walled 96-well plates (Corning) for the viability assay and 800 cells per well in 96-well Cytostar-T scintillating microplates (Amersham) for the proliferation assay. Cells were incubated for 1 day (NCI-H460) or 2 days (MCF-7, U-2 OS, and HMEC) prior to exposure to DNA-damaging agents and deacetylase inhibitors. All experiments were performed in triplicate.For viability assays, cells were treated with the indicated compounds for 48 h. Cell viability was then determined using the Cell Titer-Glo luminescent assay (Promega), which measures total ATP levels as an index of cell number. Luminescence was measured on a Luminoskan Ascent (ThermoLabSystems). |
| Concentrations | 0~100 μM |
| Incubation time | 48 h |
| Animal Experiment | |
|---|---|
| Animal models | Male Sprague-Dawley rats (8 weeks old, 200–250 g) and C57/B6 mice (8 weeks old) model |
| Formulation | DMSO |
| Dosages | 5-10 μg in a total volume of 5 μL |
| Administration | Intracerebroventricular administration |
| Molecular Weight | 248.71 |
| Formula | C13H13ClN2O |
| CAS Number | 49843-98-3 |
| Solubility (25°C) | DMSO 25 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Sirtuin Products |
|---|
| ADTL-SA1215
ADTL-SA1215 is a first-in-class, specific small molecule activator of SIRT3 that modulates autophagy in triple-negative breast cancer. |
| SIRT2/6-IN-1
SIRT2/6-IN-1 is a SIRT6/SIRT2 inhibitor, with IC50s of 106 μM and 114 μM. |
| SIRT6-IN-2
SIRT6-IN-2 is a selective SIRT6 inhibitor (IC50: 34 μM). |
| SIRT6-IN-3
SIRT6-IN-3 is a selective inhibitor of SIRT6 (IC50=7.49 μM). |
| Z26395438
Z26395438 is a potent Sirtuin-1 inhibitor, with an IC50 value of 1.6 μM. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
