2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide (AGK-2)

potent inhibitor of sirtuin 2 (SIRT2) with IC50 = 3.5 μM. Displays no activity at SIRT1 and SIRT3 at concentrations up to 40 μM

OTAVAchemicals Catalogue Number: 0117392020
CAS Registry Number: 304896-28-4
Purity: 95%+ (HPLC)

Ref.:  Kazantsev et al. Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease. Science (2007), 317, 516-519

Abstract: The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. A potent inhibitor of sirtuin 2 (SIRT2) was identified and it was found that inhibition of SIRT2 rescued α-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued α-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.