SRT2104 (GSK2245840)

Cell Assay [1]
C2C12 cell line is cultured in low glucose Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS) 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[1].

Animal Administration [1]
For the longevity study, diets are started at 28 weeks of age after randomization into two groups of 100 mice per group. Mice are fed a standard AIN-93G diet (SD; carbohydrate:protein:fat ratio of 64:19:17 percent of kcal), or a SD supplemented with SRT2104. SRT2104 is added at a dose of 1.33 g drug per kg of chow, formulated to provide daily doses of 100 mg drug/kg bodyweight. For the hindlimb suspension study, starting at 4 months of age, C57BL/6 mice are fed either a standard AIN-93G diet (SD; carbohydrate:protein:fat ratio of 64:19:17 percent of kcal) or a SD supplemented with SRT2104 for 4 weeks prior to suspension, and then for an additional 2 weeks during the suspension. Diets are formulated so mice receive a daily dose of 200 mg drug/kg of bodyweight. For the 48-h fasting study, mice are fed either SD or a SD supplemented with SRT2104 (100 mg/kg) for 6 weeks prior to sacrifice. This is the same diet as for the longevity study mice. For the whole-body SIRT1 knockout and muscle-specific SIRT1 knockout mouse models, mice are maintained on house chow (carbohydrate:protein:fat ratio of 58:24:18 percent of kcal) for the course of their lives[1].

References:
[1]. Mercken EM, et al. SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell. 2014 Oct;13(5):787-96. [2]. Jiang M, et al. Sirtuin 1 activator SRT2104 protects Huntington's disease mice. Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.