Description
EX-527 is an inhibitor of sirtuin 1 (SIRT1); sirtuins are considered class III histone deacetylases (HDACs). EX-527 binds the NAD+ site of sirtuin 1, stabilizing a closed conformation. EX-527 exhibits immunostimulatory and anti-inflammatory activities. In animal models of autoimmune colitis and inflammatory bowel disease, EX-527 increases the number of Foxp3+ Treg cells and prevents weight loss. In animal models of polycystic kidney disease, this compound delays renal cyst formation and growth. Additionally, EX-527 improves myocardial histology and increases the number of Foxp3+ Treg cells in animal models of transplant surgery, prolonging allograft survival.
References
Akimova T, Xiao H, Liu Y, et al. Targeting sirtuin-1 alleviates experimental autoimmune colitis by induction of Foxp3+ T-regulatory cells. Mucosal Immunol. 2014 Feb 19. [Epub ahead of print]. PMID: 24549276.
Gertz M, Fischer F, Nguyen GT, et al. Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism. Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):E2772-81. PMID: 23840057.
Zhou X, Fan LX, Sweeney WE Jr, et al. Sirtuin 1 inhibition delays cyst formation in autosomal-dominant polycystic kidney disease. J Clin Invest. 2013 Jul 1;123(7):3084-98. PMID: 23778143.
Beier UH, Wang L, Bhatti TR, et al. Sirtuin-1 targeting promotes Foxp3+ T-regulatory cell function and prolongs allograft survival. Mol Cell Biol. 2011 Mar;31(5):1022-9. PMID: 21199917.
