Shirakawa et al. / 1 1 Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity 2 Kotaro Shirakawa1, 2, 7, Lan Wang3, 4, Na Man3, 4, Jasna Maksimoska5, Alexander W. Sorum6, Hyung W. 3 Lim1, 2, Intelly S. Lee1, 2, Tadahiro Shimazu1, 2, John C. Newman1, 2, Sebastian Schröder1, 2, Melanie Ott1, 2, 4 Ronen Marmorstein5, Jordan Meier6, Stephen Nimer3, 4 and Eric Verdin1, 2 5 From the 1Gladstone Institutes and 2Department of Medicine, University of California, San Francisco, 6 CA 94158, 3University of Miami, Coral Gables, FL 33124, 4Sylvester Comprehensive Cancer Center, 7 Miami, FL 33136, and 5Perelman School of Medicine, University of Pennsylvania, Abramson Family 8 Cancer Research Institute and Department of Biochemistry and Biophysics, Philadelphia, PA 19104, 9 6Chemical Biology Laboratory, National Cancer Institute, Frederick, MD 21702, 7Department of 10 Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 11 Address for correspondence 12 Eric Verdin, M.D. 13 Gladstone Institutes/UCSF 14 1650 Owens Street 15 San Francisco, CA 94158 16 Tel: (415) 734-4808 17 Fax: (415) 355-0855 18 E-mail:
[email protected] 19 Running title: Salicylate and diflunisal inhibit CBP/p300 acetyltransferases 20 Keywords: salicylate, histone acetyltransferase, acetylation, diflunisal 21 Shirakawa et al. / 2 22 Abstract 23 Salicylate and acetylsalicylic acid are potent and widely used anti-inflammatory drugs. They are thought 24 to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo- 25 oxygenases, modulation of NF-κB activity, and direct activation of AMPK. However, the full spectrum of 26 their activities is incompletely understood.