1 SUPPORTING INFORMATION A Novel Series of Potent and Selective Ketone Histone Deacetylase Inhibitors with Anti-tumor Activity in vivo. Philip Jones,* Sergio Altamura, Raffaele De Francesco, Odalys Gonzalez Paz, Olaf Kinzel, Giuseppe Mesiti, Edith Monteagudo, Giovanna Pescatore, Michael Rowley, Maria Verdirame and Christian Steinkühler. IRBM/Merck Research Laboratories, Via Pontina km 30,600, 00040 Pomezia, Italy. Table of Contents Experimental section and synthetic schemes 1 HDAC Enzyme Assays 14 Protocols for cell proliferation assays 17 Protocol for plasma stability 18 Rat PK studies 19 Protocol for tumor xenograft studies 20 Experimental section and synthetic schemes General Experimental Protocols Solvents and reagents were obtained from commercial suppliers and were used without further purification. Flash chromatography purifications were performed on Merck silica gel (200-400 mesh) as the stationary phase or were conducted using prepacked cartridges on a Biotage system, eluting with petroleum ether/ethyl acetate mixtures. HPLC-MS and UPLC-MS analyses were performed on either a Waters Alliance 2795 apparatus, equipped with a diode array and a ZQ mass spectrometer using an X-Terra C18 column (5μM, 4.6x50mm) or on a Acquity UPLC TM