AK-1 is a potent, specific and cell-permeable SIRT2 inhibitor, with an IC₅₀ of 12.5 μM. In Vitro: AK-1 achieves significant neuroprotection in Huntington’s disease flies at 10 μM, improving the number of rhabdomeres from 5.2 to 5.6^[1]. AK-1 is a potent, specific and cell-permeable SIRT2 inhibitor, with an IC₅₀ of 12.5 μM^[2]. AK-1 treatment induces proteasomal degradation of the Snail transcription factor through inactivation of the NF-κB/CSN2 pathway. Reduction in the level of Snail results in upregulation of p21, leading to G1 arrest, slow proliferation, and slow wound-healing activity. The regulation of Snail-p21 axis by AK-1 also occurs in HT-29 colon cancer cells^[3]. Under hypoxic conditions, AK-1 increases the ubiquitination of HIF-1α in a VHL-dependent manner, leading to the degradation of HIF-1α via a proteasomal pathway. Downregulation of HIF-1α expression reduces its transcriptional activity and, eventually, reduces the expression of BNIP3, one of HIF-1 target genes, in AK-1-treated cells^[4].