SRT2104 (GSK2245840)

Catalog No.S7792 Batch:S779202

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Technical Data

Formula

C26H24N6O2S2
Molecular Weight 516.64 CAS No. 1093403-33-8
Solubility (25°C)* In vitro DMSO 4 mg/mL (7.74 mM)
Water Insoluble
Ethanol Insoluble
* <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.)

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Biological Activity

Description SRT2104 (GSK2245840) is a selective SIRT1 activator involved in the regulation of energy homeostasis. Phase 2.
Targets
SIRT1 [1]
In vitro SRT2104 reduces p65/RelA acetylation levels in C2C12 cells.[1]
In vivo In male C57BL/6J mice, SRT2104 (100 mg/kg, p.o.) extends both mean and maximal lifespan of mice fed a standard diet, and enhances motor coordination, bone mineral density, and insulin sensitivity and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy.[1] In Male N171-82Q HD mice, SRT2104 (diet containing 0.5% SRT2104) effectively penetrates the blood-brain barrier, attenuates brain atrophy, improves motor function, and extends survival.[2]

Protocol (from reference)

Kinase Assay:[3]
  • SIRT1 fluorescence polarization assay and HTS

    In the SIRT1 FP assay, SIRT1 activity is monitored using a 20 amino acid peptide (Ac-Glu-Glu-Lys(biotin)-Gly-Gln-Ser-Thr-Ser-Ser-His-Ser-Lys(Ac)-Nle-Ser-Thr-Glu-Gly–Lys(MR121 or Tamra)-Glu-Glu-NH2 ) derived from the sequence of p53. The peptide is N-terminally linked to biotin and C-terminally modified with a fluorescent tag. The reaction for monitoring enzyme activity is a coupled enzyme assay where the first reaction is the deacetylation reaction catalyzed by SIRT1 and the second reaction is cleavage by trypsin at the newly exposed lysine residue. The reaction is stopped and streptavidin is added in order to accentuate the mass differences between substrate and product. The fluorescence polarization reaction conditions are as follows: 0.5 μM peptide substrate, 150 μM βNAD +, 0-10 nM SIRT1, 25 mM Tris-acetate pH 8, 137 mM Na-Ac, 2.7 mM K-Ac, 1 mM Mg-Ac, 0.05% Tween-20, 0.1% Pluronic F127, 10 mM CaCl 2 , 5 mM DTT, 0.025% BSA, and 0.15 mM nicotinamide. The reaction is incubated at 37°C and stopped by addition of nicotinamide, and trypsin is added to cleave the deacetylated substrate. This reaction is incubated at 37 ℃ in the presence of 1 μM streptavidin. Fluorescent polarization is determined at excitation (650 nm) and emission (680 nm) wavelengths.
Cell Assay:[1]
  • Cell lines

    C2C12 cell line

  • Concentrations

    3 μM

  • Incubation Time

    24 h

  • Method

    Cells are cultured in low glucose Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum and penicillin–streptomycin. Cells are treated with vehicle (0.1% DMSO) or 3 μM SRT2104 for 24 h and then harvested for protein and Western blotting.
Animal Study:[2]
  • Animal Models

    Male N171-82Q HD mice

  • Dosages

    diet containing 0.5% SRT2104

  • Administration

    p.o.

Selleck's SRT2104 (GSK2245840) has been cited by 13 publications

MicroRNA-141-3p reduces pulmonary hypoxia/reoxygenation injury through suppression of Beclin-1-dependent autophagy [ Aging (Albany NY), 2024, 16(2):1352-1373] PubMed: 38261732
Neuroprotection of SRT2104 in Murine Ischemia/Reperfusion Injury Through the Enhancement of Sirt1-Mediated Deacetylation [ Invest Ophthalmol Vis Sci, 2023, 64(4):31] PubMed: 37099021
Sirtuin activation targets IDH-mutant tumors [ Neuro Oncol, 2021, 23(1):53-62] PubMed: 32710757
Design, Synthesis and Pharmacological Evaluation of Naphthofuran Derivatives as Potent SIRT1 Activators [ Front Pharmacol, 2021, 12:653233] PubMed: 33995069
SIRT1 regulates N6 -methyladenosine RNA modification in hepatocarcinogenesis by inducing RANBP2-dependent FTO SUMOylation. [ Hepatology, 2020, 10.1002/hep.31222] PubMed: 32154934
Senescent stromal cells promote cancer resistance through SIRT1 loss-potentiated overproduction of small extracellular vesicles. [ Cancer Res, 2020, 4 pii: canres] PubMed: 32366480
Poly (ADP-ribose) Polymerase 1 Inhibition Prevents Neurodegeneration and Promotes α-synuclein Degradation via Transcription Factor EB-dependent Autophagy in Mutant α-synucleinA53T Model of Parkinson's Disease [ Aging Cell, 2020, 19(6):e13163] PubMed: 32475059
Sirtuin-1 Inhibits Endothelin-2 Expression in Human Granulosa-Lutein Cells via HIF1A and Epigenetic Modifications† [ Biol Reprod, 2020, ioaa199] PubMed: 33112382
SRT2104 attenuates chronic unpredictable mild stress-induced depressive-like behaviors and imbalance between microglial M1 and M2 phenotypes in the mice. [ Behav Brain Res, 2020, 378:112296] PubMed: 31618623
Axonal protection by a small molecule SIRT1 activator, SRT2104, with alteration of autophagy in TNF-induced optic nerve degeneration. [ Jpn J Ophthalmol, 2020, 10.1007/s10384-020-00731-6] PubMed: 32157485

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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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