Structure-activity relationship study of an inhibitor of tumor metastasis

DESCRIPTION (provided by applicant): A large number of deaths from epithelial tumors of the breast, prostate, lung, ovary, liver, and kidney are caused by metastatic spread of the primary tumor. Unfortunately, there are currently no drugs on the market tha t directly target cancer cells in the process of spreading (metastasis). The tumor antigen, sialyl Lewis X (sLeX) is a glycan expressed on the surface of epithelial tumors that correlates with poor prognosis, aggressive metastasis, and death. In both human and animal studies sLeX expression can drive aggressive metastatic behavior (1-5). We have rationally designed an inhibitor of sLeX biosynthesis that potently blocks metastasis in mouse models (6-11). The following aims are focused on a structure-activity relationship study of our lead compound. PUBLIC HEALTH RELEVANCE: A large number of deaths from cancer of the breast, prostate, lung, ovary, liver, and kidney are caused by metastatic spread of the primary tumor. The medical need for an effective anti-me tastatic drug is great. These studies are aimed at optimizing an anti-metastatic drug candidate before human clinical trials.