Description
SRT1720 is an inhibitor of sirtuin 3 (SIRT3) and activator of sirtuin 1 (SIRT1); sirtuins are considered class III histone deacetylases (HDACs). SRT1720 exhibits nephroprotective, anti-aging, anti-inflammatory, and pro-angiogenic activities. SRT1720 binds the acetyl-Lys site on sirtuins rather than the NAD+ site. In animal models of kidney ischemia/reperfusion injury, SRT1720 improves renal tubular pathology and overall renal function. In animal models fed high fat diets, SRT1720 delays the onset of metabolic diseases and decreases levels of pro-inflammatory cytokines, extending animal lifespan. In animal models of macular degeneration, this compound suppresses activation of NF-κB and release of IL-6, IL-8, and MMP-9, decreasing amyloid-β (Aβ)-induced retinal pigment epithelial barrier disruption. Additionally, SRT1720 increases VEGF secretion and promotes migration and metastasis of breast cancer cells in vitro and in vivo.
References
Mitchell SJ, Martin-Montalvo A, Mercken EM, et al. The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet. Cell Rep. 2014 Mar 13;6(5):836-43. PMID: 24582957.
Cao L, Liu C, Wang F, et al. SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-κB pathway. Braz J Med Biol Res. 2013 Aug;46(8):659-69. PMID: 24036938.
Nguyen GT, Schaefer S, Gertz M, et al. Structures of human sirtuin 3 complexes with ADP-ribose and with carba-NAD+ and SRT1720: binding details and inhibition mechanism. Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1423-32. PMID: 23897466.
Fan H, Yang HC, You L, et al. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int. 2013 Mar;83(3):404-13. PMID: 23302720.
Suzuki K, Hayashi R, Ichikawa T, et al. SRT1720, a SIRT1 activator, promotes tumor cell migration, and lung metastasis of breast cancer in mice. Oncol Rep. 2012 Jun;27(6):1726-32. PMID: 22470132.
