812647-88-4

YM-08 (Compounds 7a) is a brain-penetrant inhibitors of SIRT2,with the IC50 of 19.9 μM. YM-08 also is inhibitor of Hsp70[1].

YM-08 is a Heat Shock Protein 70 (Hsp70) inhibitor that is blood-brain barrier permeable. YM-08 is a neutral derivative of the Hsp70 inhibitor MKT-077. MKT-077 reduces tau levels in cellular models, but it doesn′t penetrate the blood brain barrier. Although YM-08 was somewhat less effective than MKT-077 in anti-tau and anticancer assays, it selectively reduced pathogenic tau in brain slices, which MKT-077 did not. Furthermore,YM-08 was not retained in the kidney leading one to speculate that it would not have the nephrotoxicity that was a problem for MKT-077 in clinical trials.

HSP70

[1] Abbotto E, et al. Novel Thiazole-Based SIRT2 Inhibitors Discovered via Molecular Modelling Studies and Enzymatic Assays. Pharmaceuticals (Basel). 2023;16(9):1316. Published 2023 Sep 18. DOI:10.3390/ph16091316