Inhibitors of Heparan Sulfate Biosynthesis and Cancer

硫酸乙酰肝素生物合成抑制剂与癌症

• 批准号: 7110737
• 负责人: Charles Alexander Glass
• 金额: $ 19.62万
• 依托单位: ZACHARON PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-12 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110737
• 关键词: biosynthesis; heparan sulfate; lead; neoplasm /cancer

DESCRIPTION (provided by applicant): The underlying hypothesis of this proposal is that inhibitors of heparan sulfate biosynthesis will slow tumor growth. Genetic and pharmacological data has validated heparan sulfate as a novel anti-cancer target. This proposal describes a drug discovery program that uses two high throughput cell-based screens to identify small molecule inhibitors of heparan sulfate biosynthesis. Both assays have been validated through their ability to detect partial inhibition of heparan sulfate by chlorate, an inhibitor of macromolecular sulfation. This proposal requests funds to run the high throughput discovery screen and to characterize the lead molecules that emerge. In vitro testing of the effects on growth factor signaling will be used to determine if the compounds represent viable drug development candidates. Promising leads will be candidates for further development as novel anti-cancer drugs in a Phase II SBIR application.

描述（由申请人提供）：该提案的基本假设是硫酸乙酰肝素生物合成的抑制剂将减缓肿瘤生长。遗传和药理学数据证实硫酸乙酰肝素是一种新型抗癌靶点。该提案描述了药物发现 使用两个高通量细胞筛选来识别小分子的程序 硫酸乙酰肝素生物合成抑制剂。两种测定均已通过他们的验证 能够检测氯酸盐（一种抑制剂）对硫酸乙酰肝素的部分抑制作用 大分子硫酸化。该提案要求资金来运行高吞吐量 发现筛选并表征出现的先导分子。体外测试 对生长因子信号传导的影响将用于确定化合物是否 代表可行的药物开发候选者。有前途的潜在客户将成为候选人 在 II 期 SBIR 应用中进一步开发为新型抗癌药物。