1093403-33-8

Basic information

• Product Name: SRT2104 (GSK2245840)
• Synonyms: 5-ThiazolecarboxaMide, 4-Methyl-N-[2-[3-(4-MorpholinylMethyl)iMidazo[2,1-b]thiazol-6-yl]phenyl]-2-(3-pyridinyl)-;sirtuin Modulator;4-Methyl-N-[2-[3-(morpholinomethyl)imidazo[2,1-b]thiazol-6-yl]phenyl]-2-(pyridin-3-yl)thiazole-5-carboxamide;SRT2104 (GSK2245840);(E)-3-(3-HYDROXY-4-METHOXYPHENYL)PROP-2-ENOIC ACID;GSK2245840
• CAS NO: 1093403-33-8
• Molecular Formula: C₂₆H₂₄N₆O₂S₂
• Molecular Weight: 516.63776
• Product Categories: Inhibitors
• Mol File: 1093403-33-8.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• Density: 1.46±0.1 g/cm3(Predicted)
• Solubility: insoluble in H2O; insoluble in EtOH; ≥6.46 mg/mL in DMSO with gentle warming
• PKA: 11.40±0.70(Predicted)
• CAS DataBase Reference: SRT2104 (GSK2245840)(CAS DataBase Reference)
• NIST Chemistry Reference: SRT2104 (GSK2245840)(1093403-33-8)
• EPA Substance Registry System: SRT2104 (GSK2245840)(1093403-33-8)

Safety Data

• Hazardous Substances Data: 1093403-33-8(Hazardous Substances Data)

Usage

Biological Activity

srt2104 (gsk2245840) is a selective sirt1 activator involved in the regulation of energy homeostasis. sirt1, also known as nad-dependent deacetylase sirtuin-1, is a member of the sirtuin family of proteins.

in vitro

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 [1].

in vivo

in male c57bl/6j mice, administration of srt2104 (100 mg/kg, p.o.) extended both mean and maximal lifespan of mice fed a standard diet, and enhanced bone mineral density, motor coordination, and insulin sensitivity and decreased inflammation. short-term srt2104 administration preserved bone and muscle mass in an experimental model of atrophy [1]. in male n171-82q hd mice with huntington's disease, srt2104 (diet containing 0.5% srt2104) effectively penetrated the blood-brain barrier, attenuated brain atrophy, improved motor function, and extended survival [2].

references

[1]. mercken e m, mitchell s j, martin‐montalvo a, et al. srt2104 extends survival of male mice on a standard diet and preserves bone and muscle mass[j]. aging cell, 2014, 13(5): 787-796.[2]. jiang m, zheng j, peng q, et al. sirtuin 1 activator srt2104 protects huntington's disease mice[j]. annals of clinical and translational neurology, 2014, 1(12): 1047-1052.

Upstream product

• 39091-01-5 4-methyl-2-(pyridin-3-yl)-5-thiazolecarboxylic acid 
• 6851-99-6 2-bromo-1-(2-nitrophenyl)ethanone 
• 1093403-37-2 C₁₃H₁₁N₃O₅S₂ 
• 912770-13-9 6-(2-nitro-phenyl)-imidazo[2,1-b]thiazole-3-carboxylic acid 
• 925437-84-9 6-(2-nitrophenyl)-imidazo[2,1-b]thiazole-3-carboxylic acid ethyl ester 
• 1056562-54-9 2-(3-morpholin-4-ylmethyl-imidazo[2,1-b]thiazol-6-yl)-phenylamine 
• 925437-85-0 (6-(2-nitrophenyl)imidazo[2,1-b]thiazol-3-yl)methanol 
• 925438-48-8 3-chloromethyl-6-(2-nitro-phenyl)-imidazo[2,1-b]thiazole 
• 62529-67-3 4-methyl-2-pyridin-3-yl-thiazol-5-carboxylic acid chloride 

Relevant articles and documents

The identification of the SIRT1 activator SRT2104 as a clinical candidate

We have identified SRT2104 (4) as the first direct synthetic SIRT1 activator clinical candidate. The compound was derived from the optimization of a previously described imidazo[1,2-b]thiazole scaffold. SRT2104 was selected as a development candidate based on a combination of biochemical activity and pharmacokinetic profile. The in vivo characteristics of SRT2104 were superior to those of analogues with similar activation profiles. The overall preclinical profile suggests that the compound has potential to provide therapeutic benefit in a clinical setting. 2013 Bentham Science Publishers.