Structure-activity relationship study of an inhibitor of tumor metastasis

肿瘤转移抑制剂的构效关系研究

• 批准号: 7480179
• 负责人: Jillian R Brown
• 金额: $ 18.81万
• 依托单位: ZACHARON PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-12 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480179
• 关键词: Anabolism; Animals; Behavior; Cessation of life; Clinical Trials; Epithelial; Galactose; Human; In Vitro; Kidney; Lead; Liver; Lung; Mammary Neoplasms; Marketing; Medical; Neoplasm Metastasis; Numbers; Ovary; Pharmaceutical Preparations; Polysaccharides; Primary Neoplasm; Process; Product R; Property; Prostate; Public Health; Structure-Activity Relationship; Surface; Testing; Toxicology; Tumor Antigens; analog; cancer cell; design; inhibitor/antagonist; malignant breast neoplasm; mouse model; outcome forecast; tumor

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.

描述（由申请人提供）：乳房，前列腺，肺，卵巢，肝脏和肾脏的大量死亡是由原发性肿瘤的转移扩散引起的。不幸的是，目前市场上没有药物在扩散过程中直接靶向癌细胞（转移）。肿瘤抗原Siallyl Lewis X（SLEX）是在上皮肿瘤表面表达的聚糖，与预后不良，侵略性转移和死亡相关。在人类和动物研究中，SLEX表达都可以推动侵略性转移行为（1-5）。我们已经合理地设计了一种SLEX生物合成的抑制剂，该抑制剂可在小鼠模型中有效地阻断转移（6-11）。以下目标集中在我们铅化合物的结构活性关系研究上。 公共卫生相关性：乳腺癌，前列腺，肺，卵巢，肝脏和肾脏的大量死亡是由原发性肿瘤的转移扩散引起的。有效的抗转移药物的医疗需求很大。这些研究的目的是在人类临床试验之前优化抗转移性药物候选者。