Selectively inhibit sirtuin 2 (SIRT2) with AK-7, a neuroprotective agent (IC50 = 15.5 μM; Chen et al.). SIRT2 is a deacetylase that targets histone 4, α-tubulin, forkhead transcription factors of class O (FOXO), and other protein substrates. Because its activity regulates many cellular processes, SIRT2 has been connected to cancer, age-related disorders, and neurodegenerative diseases (de Oliveira et al.). As an inhibitor of SIRT2, AK-7 reduces neuronal death in Huntington’s disease (HD) mouse models (Chopra et al.). AK-7 is inactive against SIRT1 and SIRT3 (Taylor et al.).

AK-7 has been used for:

DISEASE MODELING
· Protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity and α‐Synuclein (aSyn) toxicity in Parkinson’s disease mouse models (Chen et al.).
· Promotes neuronal survival in Huntington’s disease mouse models (Chopra et al.).
· Improves the outcome of brain ischemia in mice by reportedly enhancing P38 activation levels in vitro and in vivo, significantly decreasing infarction volume, as well as promoting the recovery of neurological function in mice evaluated in behavior tests (Wu et al.).
· Decreases cochlear cell apoptosis and attenuates noise-induced hearing loss, as well as reduces oxidative nuclear DNA damage and apoptosis in mouse cochlea following noise exposure. AK-7 has also been shown to reduce apoptosis of mouse inner ear HEI-OC1 cells exposed to oxidative stress in vitro (Liu et al.).