product name SRT2104 (GSK2245840)
Description: SRT2104, also known as GSK2245840, is a novel, first-in-class, highly selective small molecule activator of SIRT1 involved in the regulation of energy homeostasis. SRT2104 has been developed as a selective small molecule activator of SIRT1, a NAD(+)-dependent deacetylase involved in the regulation of energy homeostasis and the modulation of various metabolic pathways, including glucose metabolism, oxidative stress and lipid metabolism.
References: Aging Cell. 2014 Oct;13(5):787-96; Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.
516.64
Formula
C26H24N6O2S2
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
Solubility (In vivo)
Synonyms
other peoduct :
| 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 Dulbeccos modified Eagles 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. |
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| 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. 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 model | Male N171-82Q HD mice |
| Formulation & Dosage | Taken with diet containing 0.5% SRT2104; p.o. |
| References | Aging Cell. 2014 Oct;13(5):787-96; Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52. |
