生物活性

• 描述Sirtuin 2 is a member of the sirtuin family of proteins. It is a NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Sirtuin 2 participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. It also plays a major role in the control of cell cycle progression and genomic stability. AK-7 is a Sirtuin 2 selective inhibitor with IC₅₀ of 15.5μM. At the concentration of 10μM, AK-7 reduced cholesterol levels in naive N2a neuroblastoma cells and hippocampal slice cultures from wild-type mice. At the concentration of 1μM , AK-7 showed neuroprotective effect in striatal Huntington's disease neurons^[3]. When i.p. administrated at the dose of 10mg/kg or 20mg/kg, AK-7 improved the behavior and neuropathological phenotype and extended survival of R6/2 HD mice. At the dose of 20mg/kg, AK-7 ameliorated HD neuropathology in R6/2 mice^[4]. At the dose of 20mg/kg, i.p. administrated AK7 was neuroprotective in a subacute MPTP mouse model of Parkinson's disease and significant increase of α-tubulin aectylation in the striatum after AK7 treatment was confirmed^[5].
• 作用机制AK-7 is a Sirtuin 2 selective inhibitor with a NAD⁺ competitive mechanism. The binding of AK-7 to Sirtuin 2 was suggested through docking calculations^[5].