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bioRxiv · 10.1101/2020.03.20.000380

Selective inhibitors of SIRT2 regulate perinuclear α-tubulin acetylation, migration, and invasion of breast cancer cells

Nielsen, A. L.·Rajabi, N.·Kudo, N.·Larsen, K. L.·Fontenas, M.·Lucidi, A.·Madsen, A. S.·Yoshida, M.·Olsen, C. A.
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Abstract

Sirtuin 2 (SIRT2) is a protein deacylase enzyme that removes acetyl groups and longer chain acyl groups from post-translationally modified lysine residues. It affects diverse biological functions in the cell and has been considered a drug target in relation to both neurodegenerative diseases and cancer. Therefore, access to well-characterized and robust tool compounds is essential for the continued investigation of the complex functions of this enzyme. Here, we report a collection of probes that are potent, selective, stable in serum, water-soluble, amenable to cell culture experiments, and inhibit both SIRT2 deacetylation and demyristoylation. Compared to the current landscape of SIRT2 inhibitors, this is a unique ensemble of features built into a single compound. We expect the developed chemotypes to find broad application in the interrogation of SIRT2 functions in both healthy and diseased cells, and to provide a foundation for the development of future therapeutics.

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Nielsen, A. L., Rajabi, N., Kudo, N., Larsen, K. L., Fontenas, M., Lucidi, A., Madsen, A. S., Yoshida, M., Olsen, C. A.. 2020-03-22. Selective inhibitors of SIRT2 regulate perinuclear α-tubulin acetylation, migration, and invasion of breast cancer cells. https://doi.org/10.1101/2020.03.20.000380

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