SRT 2104

Names

[ Name ]:
SRT 2104

[Synonym ]:
4-methyl-N-(2-(3-(morpholinomethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)-2-(pyridin-3-yl)thiazole-5-carboxamide
CS-0955
5-Thiazolecarboxamide, 4-methyl-N-[2-[3-(4-morpholinylmethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]-2-(3-pyridinyl)-
5-Thiazolecarboxamide,4-methyl-N-[2-[3-(4-morpholinylmethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]-2-(3-pyridinyl)
4-Methyl-N-{2-[3-(4-morpholinylmethyl)imidazo[2,1-b][1,3]thiazol-6-yl]phenyl}-2-(3-pyridinyl)-1,3-thiazole-5-carboxamide
sirtuin modulator
SRT 2104
GSK2245840
SRT-2104

Biological Activity

[Description]:

SRT 2104 is a brain-permeable activator of SIRT1, used for the research of type 2 diabetes mellitus and Huntington's disease.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Sirtuin

Signaling Pathways >> Epigenetics >> Sirtuin

Research Areas >> Cancer

[Target]

SIRT1

[In Vitro]

SRT 2104 (3 μM) reduces p65/RelA acetylation levels in C2C12 cells[1].

[In Vivo]

SRT2104 (100 mg/kg, p.o.) improves whole-body physiology and extends lifespan in mice fed a standard diet. SRT2104 increases mitochondrial content and suppresses the inflammatory response in SD-fed mice. SRT2104 also changes the gene expression profile differently in liver and muscle. Short-term SRT2104 preserves muscle and bone mass[1]. 0.5% SRT2104 diet penetrates the blood-brain barrier, attenuates brain atrophy, improves motor function, and extends survival in a mouse model of Huntington's disease[2].

[Cell Assay]

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 admin]

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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Molecular Formula ]:
C₂₆H₂₄N₆O₂S₂

[ Molecular Weight ]:
516.638

[ Exact Mass ]:
516.140198

[ PSA ]:
144.62000

[ LogP ]:
4.10

[ Index of Refraction ]:
1.761

[ Storage condition ]:
-20℃

SRT 2104

Names

Biological Activity

Chemical & Physical Properties

Related Compounds