Description

• A cell-permeable S-isobutyryl prodrug that is processed intracellularly to form the potent HDAC inhibitor NCH-31 (IC USB>50 = 48 and 170 nM, respectively, using partially purified HDAC1 or HeLa nuclear extract) that is predicted to exhibit a similar HADC binding mode as that of SAHA with its sulfhydryl replacing SAHA's hydroxamate as the active-site zinc-targeting group
• NCH-51 is shown to exhibit comparable antiproliferative (mean IC 50 = 3.8μM vs
• 3.7μM for SAHA; 48 h treatment) and apoptotic activity as SAHA against various cancer cell lines, but not PBMCs from 4 healthy individuals (IC 50 >30μM with either drug), and the antioxidant N-Acetyl-L-Cysteine (NAC; Cat
• No
• 106425) at 2mm is reported to abolish the cell-growth inhibition caused by either 3μM NCH-51 or SAHA in the Multiple Myeloma U266 cultures
• Half-life in human plasma at 37 °C = 24 h.