AK-7

AK-7 is a selective, brain-permeable small molecule inhibitor of sirtuin 2 (SIRT2), an NAD-dependent deacetylase implicated in cytoskeletal regulation, neuronal survival, and neurodegenerative disease progression. It exhibits high selectivity for SIRT2 (IC50 ≈ 15.5 μM), without detectable activity toward SIRT1 or SIRT3. Mechanistically, AK-7 occupies the NAD+ binding site of SIRT2, acting as a competitive inhibitor with respect to NAD+ but not the acetylated peptide substrate. In cellular and animal models, AK-7 displays neuroprotective effects, particularly in models of Parkinson's disease and Huntington's disease, where it reduces neurodegeneration, prevents dopamine depletion, decreases α-synuclein toxicity, and improves motor function and survival. However, it has shown no protective effects in models of amyotrophic lateral sclerosis (ALS) or cerebral ischemia. AK-7 also down-regulates cholesterol biosynthesis genes in neurons and lowers neuronal cholesterol levels. Developed for research purposes, AK-7 is brain-penetrant and used to study SIRT2-mediated pathways in neurodegeneration[1][2][3][4][5].

Other names

3-(1-Azepanylsulfonyl)-N-(3-bromophenyl)benzamide