Structure-activity relationship study of an inhibitor of tumor metastasis

描述(申请人提供)：大量死于乳腺、前列腺、肺、卵巢、肝脏和肾脏的上皮性肿瘤是由原发肿瘤的转移性扩散引起的。不幸的是，目前市场上还没有直接针对扩散(转移)过程中的癌细胞的药物。肿瘤抗原唾液酸化路易斯X(sialyl Lewis X，SLeX)是一种表达在上皮性肿瘤表面的糖蛋白，与不良预后、侵袭性转移和死亡有关。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)。我们合理地设计了一种SLeX生物合成的抑制剂，可以有效地阻断小鼠模型中的转移(6-11)。本论文的主要目的是研究先导化合物的构效关系。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扩散引起的。医学上非常需要一种有效的抗转移药物。这些研究的目的是在人类临床试验之前优化一种抗转移药物候选药物。

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.