Structure-activity relationship study of an inhibitor of tumor metastasis

描述（由申请人提供）：大量因乳腺、前列腺、肺、卵巢、肝脏和肾脏上皮性肿瘤而死亡的病例是由原发肿瘤的转移扩散引起的。不幸的是，目前市场上还没有直接针对癌细胞扩散（转移）过程的药物。肿瘤抗原，sialyl Lewis X （sLeX）是一种在上皮性肿瘤表面表达的聚糖，与预后不良、侵袭性转移和死亡相关。在人类和动物研究中，sLeX的表达可以驱动侵袭性转移行为（1-5）。我们合理设计了一种sLeX生物合成抑制剂，可以有效地阻断小鼠模型中的转移（6-11）。下面的目的是集中在我们的先导化合物的构效关系的研究。公共卫生相关性：大量乳腺癌、前列腺癌、肺癌、卵巢癌、肝癌和肾癌的死亡是由原发肿瘤的转移性扩散引起的。医学上对有效的抗转移药物的需求是巨大的。这些研究的目的是在人类临床试验之前优化抗转移药物。

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.