Developing targeted cancer therapies typically starts with the identification of oncoproteins that are mutated or over-activated in tumors, followed by the development of small molecules that target the oncoproteins. A paradigm example is the development of Gleevec targeting the BCR-ABL oncoprotein in chronic myeloid leukemia. Many other targeted therapies follow this logic, such as compounds that target RAS mutants or overexpressed Myc (reviewed in [1]). We recently developed a potent and selective SIRT2 inhibitor, TM, which exhibits broad anticancer activity partly by decreasing the protein level of Myc (Figure ​(Figure1)1) [2]. Here we summarize several lessons we learned from this study with the intention that they may help other researchers developing targeted cancer therapies.