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

Uses

AGK2 is a SIRT2 inhibitor. AGK2 has been used in a study to determine that SIRT2 inhibition induces cell death and decreases the intracellular ATP level. AGK2 also rescues dopamine neurons from α-synuclein toxicity in Parkinson′s disease models.

Definition

ChEBI: 2-cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-(5-quinolinyl)-2-propenamide is a member of quinolines.

Biological Activity

Selective inhibitor of SIRT2 (IC 50 = 3.5 μ M). Displays no activity at SIRT1 and SIRT3 at concentrations up to 40 μ M. Reduces α -synuclein-mediated toxicity in in vitro and in vivo models of Parkinson's disease.

Biochem/physiol Actions

AGK2 is a SIRT2 inhibitor. AGK2 rescues dopamine neurons from α-synuclein toxicity in Parkinson′s disease models. IC50 for SIRT2 = 3.5 uM. AGK2 is >15-fold more selective for SIRT2 than SIRT1 and SIRT3. AGK2 may be the most selective SIRT2 inhibitor available.

References

[1]. outeiro tf, kontopoulos e, altmann sm, et al. sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of parkinson's disease. science, 2007, 317(5837): 516-519.
[2]. scuderi c, stecca c, bronzuoli mr, et al. sirtuin modulators control reactive gliosis in an in vitro model of alzheimer's disease. front pharmacol, 2014, 5: 89.
[3]. rotili d, tarantino d, nebbioso a, et al. discovery of salermide-related sirtuin inhibitors: binding mode studies and antiproliferative effects in cancer cells including cancer stem cells. j med chem, 2012, 55(24): 10937-10947.