2. Academic Validation
  3. A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity

A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity

  • Cancer Cell. 2016 Mar 14;29(3):297-310. doi: 10.1016/j.ccell.2016.02.007.
Hui Jing 1,  Jing Hu 1,  Bin He 1,  Yashira L Negrón Abril 2,  Jack Stupinski 2,  Keren Weiser 3,  Marisa Carbonaro 3,  Ying-Ling Chiang 1,  Teresa Southard 2,  Paraskevi Giannakakou 3,  Robert S Weiss 2,  Hening Lin 4
Affiliations

Affiliations

  • 1 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • 2 Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
  • 3 Division of Hematology & Medical Oncology, Weill Medical College of Cornell University, 1300 York Avenue, C610C, New York, NY 10065-4896, USA.
  • 4 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. Electronic address: hl379@cornell.edu.
PMID: 26977881 DOI: 10.1016/j.ccell.2016.02.007
Abstract

Targeting sirtuins for Cancer treatment has been a topic of debate due to conflicting reports and lack of potent and specific inhibitors. We have developed a thiomyristoyl lysine compound, TM, as a potent SIRT2-specific inhibitor with a broad Anticancer effect in various human Cancer cells and mouse models of breast Cancer. Mechanistically, SIRT2 inhibition promotes c-Myc ubiquitination and degradation. The Anticancer effect of TM correlates with its ability to decrease c-Myc level. TM had limited effects on non-cancerous cells and tumor-free mice, suggesting that Cancer cells have an increased dependency on SIRT2 that can be exploited for therapeutic benefit. Our studies demonstrate that SIRT2-selective inhibitors are promising Anticancer agents and may represent a general strategy to target certain c-Myc-driven cancers.

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