Sirtinol

Catalog No.S2804 Batch:S280401

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Technical Data

Formula

C26H22N2O2
Molecular Weight 394.47 CAS No. 410536-97-9
Solubility (25°C)* In vitro DMSO 23 mg/mL (58.3 mM)
Water Insoluble
Ethanol Insoluble
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
2%DMSO 30%PEG300 5%Tween80 63%ddH2O

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 0.400mg/ml (1.01mM) Taking the 1 mL working solution as an example, add 20 μL of 20 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 630 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.)

Preparing Stock Solutions

Biological Activity

Description Sirtinol is a specific SIRT1 and SIRT2 inhibitor with IC50 of 131 5M and 38 5M in cell-free assays, respectively.
Targets
SIRT2
(Cell-free assay)		 SIRT1
(Cell-free assay)
38 μM 131 μM
In vitro Sirtinol potently inhibits recombinant yeast Sir2p activity in vitro with IC50 of 68 5M. Unlike TSA, this compound has shown no effect on human HDAC1, indicating that it is a selective Sirtuin inhibitor. Unlike TSA, treatment of human primary fibroblasts with this chemical does not cause global changes in acetylation of histones and tubulin, nor does it induce a morphological change in the HeLa tumour cell line. Treatment with this inhibitor at 100 5M for 24 hours causes a sustained growth arrest in MCF-7 and H1299 cells for up to 9 days after its withdrawal. This treatment induces increased SA-2-gal activity and expression of PAI-1 in both MCF-7 and H1299 cells, more potently than Splitomicin. It inhibits colony formation at concentrations of 33 5M and higher in MCF-7 and H1299 cells, more effectively compared with Splitomicin. This compound (100 5M) significantly attenuates both basal and EGF- or IGF-I-stimulated phosphorylation of ERK, JNK/SAPK and p38 MAPK in MCF-7 and H1299 cells. It blocks the basal and EGF-stimulated activation of Ras. Consistent, basal and EGF- or IGF-I-stimulated phosphorylation of Raf-1, MEK, SEK1/MKK4 and MKK7 is attenuated in cells treated with this inhibitor. Inhibition of Sirt1 by this chemical enhances UV- and H2O2-induced p53 acetylation to enhance cell death in cultured skin keratinocytes. Blocking of Sirt1 by this treatment results in a significant inhibition in the growth and viability of human PCa cells while having no effect on normal prostate epithelial cells.
In Vivo Administration of Sirtinol at 1 mg/kg attenuates pro-inflammatory cytokine production and protects against hepatic injury following trauma-haemorrhage in male Sprague-Dawley rats.
Features Sirtinol does not inhibit class I and class II HDACs.

Protocol (from reference)

Kinase Assay:

[1]
  • Inhibition in vitro of human Sirt2 activity

    1.5 5g of recombinant human GST-Sirt2 (amino acids 18-340) are incubated at 300C for 2 hours in 50 5L of assay buffer (50 mM Tris-HCl, pH 8.8, 4 mM MgCl2, 0.2 mM dithiothreitol with different concentrations of Sirtinol, 50 5M NAD, and tritiated acetylated HeLa histones (1000 cpm), purified by acid extraction. HDAC activity is determined by scintillation counting of the ethyl acetate-soluble [3H]acetic acid.
Cell Assay:

[7]
  • Cell Lines

    LNCaP, 22Rv1, DU145, and PC3

  • Concentrations

    Dissolved in DMSO, final concentrations ~120 μM

  • Incubation Time

    24 or 48 hours

  • Method

    Cells are grown to 60% confluence and then treated with 30 μM or 120 μM sirtinol for 24 or 48 hours. Cells are trypsinized and collected. The cells are pelleted by centrifugation and resuspended in PBS (120 μL). Trypan blue (0.4% in PBS; 10 μL) is added to a smaller aliquot (10 μL) of cell suspension, and the number of cells (viable unstained and nonviable blue) are counted.
Animal Study:

[4]
  • Animal Models

    Male Sprague-Dawley rats subjected to trauma-hemorrhage

  • Dosages

    1 mg/kg

  • Administration

    Administered intravenously

References

  • https://pubmed.ncbi.nlm.nih.gov/11483616/
  • https://pubmed.ncbi.nlm.nih.gov/16302818/
  • https://pubmed.ncbi.nlm.nih.gov/16170353/
  • https://pubmed.ncbi.nlm.nih.gov/18419717/
  • https://pubmed.ncbi.nlm.nih.gov/18573234/
  • https://pubmed.ncbi.nlm.nih.gov/18681908/
  • https://pubmed.ncbi.nlm.nih.gov/19075016/
  • https://pubmed.ncbi.nlm.nih.gov/21454220/

Customer Product Validation

Effects of sirtinol on SIRT1 expression and HIF-1α. hMSCs were treated with sirtinol (100 uM) or equivalent concentration of DMSO (CTR) for 24 h and then exposed to 1% O2 for 6 h. All cells lysates were analyzed for SIRT1, HIF-1α, and tubulin by Western blot.

Data from [ Biomed Res Int , 2014 , 783459 ]

SIRT1 is involved in GABA-mediated protection against apoptosis and induction of insulin secretion. INS-1 cells are protected from apoptosis induced by tacrolimus (FK506; panel A) or streptozotocin (STZ, panel B) by GABA, and the protective effect is reversed by EX527 (SIRT1 inhibitor) or sirtinol (SIRT1 and SIRT2 inhibitor). The cells were incubated with GABA (100 uM), EX527 (200 nM) or sirtinol (4 uM) as indicated, for 1 h before adding 1 uM FK506, and cell viability was tested after 48 h. Similarly, STZ (2 mM) was added after the cells were incubated with other reagents for 1 h, but was replaced with the original medium containing all additives and no STZ after 1 h incubation. Viable cells were counted after 24 h. The results are representative of two experiments.

Data from [ Biochem Biophys Res Commun , 2014 , 452(3), 649-54 ]

Effects of Cap pretreatment with or without coadministration of sirtinol on the activities of caspase-3 in the rat primary cardiomyocytes after A/R. A/R induced a significant increase in the activities of caspase-3. Cap significantly decreased the change in the activities of caspase-3 caused by A/R, and sirtinol significantly blocked the effects of Cap. Values were expressed as the mean ± SEM (n = 6). ∗∗P < 0.01 versus the control group; ▲▲P < 0.01 versus the A/R group; ##P < 0.01 versus the Cap + A/R group.

Data from [ , , Oxid Med Cell Longev, 2017, 2017:1035702 ]

PC12 cells were treated with Sirtinol (50 μm for 24 h) and immunoblotted with the indicated antibodies.

Data from [ , , Sci Rep, 2016, 6:21857 ]

Sellecks Sirtinol Has Been Cited by 44 Publications

α-Mangostin Inhibited M1 Polarization of Macrophages/Monocytes in Antigen-Induced Arthritis Mice by Up-Regulating Silent Information Regulator 1 and Peroxisome Proliferators-Activated Receptor γ Simultaneously [ Drug Des Devel Ther, 2023, 17:563-577] PubMed: 36860800
A COMPARATIVE ANALYSIS TO DETERMINE THE OPTIMUM HISTONE DEACETYLASE INHIBITORS AND ADMINISTRATION ROUTE FOR IMPROVING SURVIVAL AND ORGAN INJURY IN RATS AFTER HEMORRHAGIC SHOCK [ Shock, 2023, 60(1):75-83] PubMed: 37141162
Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis [ Surg Open Sci, 2023, 12:35-42] PubMed: 36936452
Epigenetic alterations of CXCL5 in Cr(VI)-induced carcinogenesis [ Sci Total Environ, 2022, 838(Pt 1):155713] PubMed: 35660107
Targeting the MITF/APAF-1 axis as salvage therapy for MAPK inhibitors in resistant melanoma [ Cell Rep, 2022, 41(6):111601] PubMed: 36351409
Nicotinamide improves in vitro lens regeneration in a mouse capsular bag model [ Stem Cell Res Ther, 2022, 13(1):198] PubMed: 35550648
Effects of Hst3p inhibition in <i>Candida albicans</i>: a genome-wide H3K56 acetylation analysis [ Front Cell Infect Microbiol, 2022, 12:1031814] PubMed: 36389164
Nicotinamide n-Oxide Attenuates HSV-1-Induced Microglial Inflammation through Sirtuin-1/NF-κB Signaling [ Int J Mol Sci, 2022, 23(24)16085] PubMed: 36555725
Arylamine N-Acetyltransferase 1 Activity is Regulated by the Protein Acetylation Status [ Front Pharmacol, 2022, 13:797469] PubMed: 35153780
Screening Health-Promoting Compounds for Their Capacity to Induce the Activity of FOXO3 [ J Gerontol A Biol Sci Med Sci, 2022, 77-8:1485-1493] PubMed: 34508571

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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