Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 39, Issue 10, Pages 1739-1742Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b16-00520
Keywords
SIRT2; c-Myc; breast cancer; high-throughput screening; eukaryotic translation initiation factor 5A
Categories
Funding
- Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology of Japan
- CREST Research Project of the Japan Agency for Medical Research and Development (AMED)
- Japan Society for the Promotion of Science (JSPS)
- Project for Development of Innovative Research on Cancer Therapeutics (P-Direct)
Ask authors/readers for more resources
SIRT2 is a member of the human sirtuin family of proteins and possesses nicotinamide adenine dinucleotide (NAD)-dependent lysine deacetylase activity. SIRT2 has been involved in various cellular processes including gene transcription, genome constancy, and the cell cycle. In addition, SIRT2 is deeply implicated in diverse diseases including cancer. In this study, we identified a small molecule inhibitor of SIRT2 with a structure different from known SIRT2 inhibitors by screening from a chemical library. The hit compound showed a high selectivity toward SIRT2 as it only inhibited SIRT2, and not other sirtuins including SIRT1 and SIRT3 or zinc -dependent histone deacetylases (HDACs) including HDAC1 and HDAC6, in vitro. The compound increased the acetylation level of eukaryotic translation initiation factor 5A (eIF5A), a physiological substrate of SIRT2, and reduced cell viability of human breast cancer cells accompanied with a decrease in c-Myc expression. These results suggest that the compound is cellular effective and has potential for development as a therapeutic agent against breast cancers by specific inhibition of SIRT2.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available