Structure-activity relationship study of an inhibitor of tumor metastasis

描述（由申请人提供）：乳腺、前列腺、肺、卵巢、肝脏和肾脏上皮性肿瘤的大量死亡是由原发肿瘤的转移性扩散引起的。不幸的是，目前市场上没有直接靶向扩散（转移）过程中的癌细胞的药物。肿瘤抗原唾液酸刘易斯X（sLeX）是在上皮肿瘤表面上表达的聚糖，其与不良预后、侵袭性转移和死亡相关。在人类和动物研究中，sLeX表达可以驱动侵袭性转移行为（1-5）。我们已经合理地设计了sLeX生物合成的抑制剂，其在小鼠模型中有效地阻断转移（6-11）。以下目的是集中在我们的先导化合物的构效关系研究。 公共卫生相关性：乳腺癌、前列腺癌、肺癌、卵巢癌、肝癌和肾癌的大量死亡是由原发肿瘤的转移性扩散引起的。对有效的抗转移药物的医学需求是巨大的。这些研究旨在在人体临床试验之前优化抗转移候选药物。

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 that 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-metastatic drug is great. These studies are aimed at optimizing an anti-metastatic drug candidate before human clinical trials.