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    SRT2104 (GSK-2245840)
    SRT2104 (GSK-2245840)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0438
    CAS #: 1093403-33-8Purity ≥98%

    Description: SRT2104 (formerly GSK-2245840; SRT2104; GSK2245840; SRT-2104) is a novel, first-in-class, brain penetrant, and highly selective small molecule activator of SIRT1 (Sirtuin 1) with potential use for neurodegenerative diseases. SIRT1 (Sirtuin 1) is involved in the regulation of energy homeostasis. Sirtuin 1 is a nicotinamide adenine dinucleotide-dependent protein deacetylase which regulates longevity and improves metabolism. Activation of Sirtuin 1 confers beneficial effects in models of neurodegenerative diseases. SRT2104 can penetrate the blood-brain barrier, attenuate brain atrophy, improve motor function, and extend survival in a mouse model of Huntington's disease. These findings imply a novel therapeutic strategy for Huntington's disease by targeting Sirtuin 1.

    References: Aging Cell. 2014 Oct;13(5):787-96; Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.

    Publications Citing Use of InvivoChem SRT2104 (GSK-2245840):  

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    Molecular Weight (MW)516.64
    CAS No.1093403-33-8
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 16 mg/mL (31.0 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL

    GSK2245840; SRT2104; GSK-2245840; SRT 2104; GSK 2245840; SRT-2104.

    Chemical Name: 4-methyl-N-(2-(3-(morpholinomethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)-2-(pyridin-3-yl)thiazole-5-carboxamide

    SMILES Code: O=C(C1=C(C)N=C(C2=CC=CN=C2)S1)NC3=CC=CC=C3C4=CN5C(SC=C5CN6CCOCC6)=N4 

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    In Vitro

    In vitro activity: In C2C12 myoblasts stably transfected with small hairpin RNA to knock-down SIRT1, SRT2104 increased AP activity, a marker for osteogenic differentiation. This effect was totally dependent on SIRT1 expression.

    Kinase Assay: 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: Cells  (C2C12 cell line) 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.

    In VivoIn 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. 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.
    Animal modelMale N171-82Q HD mice
    Formulation & DosageTaken with diet containing 0.5% SRT2104; p.o.

    Aging Cell. 2014 Oct;13(5):787-96; Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.

    These protocols are for reference only. InvivoChem does not independently validate these methods.

    SRT2104 (GSK2245840)

    SRT2104 treatment improves whole-body physiology and extends lifespan in mice fed a standard diet.  2014 Oct;13(5):787-96.

    SRT2104 (GSK2245840)

    SRT2104 changes the gene expression profile differently in liver and muscle.  2014 Oct;13(5):787-96.

    SRT2104 (GSK2245840)

    SRT2104 treatment increases mitochondrial content and suppresses the inflammatory response.  2014 Oct;13(5):787-96.

    SRT2104 (GSK2245840)

    Short-term SRT2104 treatment preserves muscle and bone mass.  2014 Oct;13(5):787-96.

    SRT2104 (GSK2245840)

    SRT2104 ameliorated motor deficits and increased survival in N171-82Q HD mice.  2014 Dec;1(12):1047-52.


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