The main commercial goal of our company is to develop novel therapeutics to inhibit the human oncogene, c-Myc. C-Myc is a major human oncogene that is estimated to contribute to at least 70% of all human cancers, most of which are aggressive and respond poorly to current therapies. Despite more than 30 years of research on c-Myc, the development of drugs that inhibit c-Myc has been unsuccessful because the protein is a transcription factor that lacks pockets for small molecules to bind. Therefore, developing novel treatments that inhibit c-Myc is considered one of the most important goals for advancing cancer therapeutics. Recently studies from several laboratories, including ours, have shown that the small ubiquitin-like modifications (SUMO) are critical for c-Myc- dependent tumorigenesis. Therefore, our research has focused on inhibiting c-Myc by targeting SUMOylation. Our initial studies are focused on colorectal cancers, because nearly 100% of these cancers depend on c-Myc, and new therapies are critically needed for metastatic colorectal cancers to improve patient survival. SUMOylation is important for c-Myc expression by activating - catenin/Tcf-4, the key transcription factor for inducing c-Myc expression in colorectal cancers. We have successfully completed the studies proposed for our Phase I SBIR award and have developed a new series of lead compounds that have improved potency and specificity. In Phase II studies, we propose to conduct necessary pharmacology formulation development, Chemistry, Manufacturing and Controls work, and IND-enabling studies. At the completion of these preclinical Phase II studies we anticipate being prepared to file an IND application to support further progress toward clinical trials. Ultimately, development of effective c-Myc-inhibiting drug would be paradigm-shifting for cancer treatment and fill a major void in the market.