Inhibitors of Heparan Sulfate Biosynthesis and Cancer

描述（由申请人提供）：该提议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。遗传学和药理学数据已经证实硫酸乙酰肝素是一种新的抗癌靶点。这个提案描述了一个药物发现 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的抑制剂。两种检测方法均已通过其 检测氯酸盐对硫酸乙酰肝素的部分抑制的能力， 大分子硫酸化该提案要求资金运行高吞吐量 发现屏幕和表征出现的铅分子。的体外测试 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人。有前途的线索将成为候选人， 进一步开发为II期SBIR应用中的新型抗癌药物。

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.