Development of cell-based assays for discovery of GIcNAc-TV inhibitors.

开发基于细胞的检测方法来发现 GlcNAc-TV 抑制剂。

• 批准号: 7171648
• 负责人: BRETT E CRAWFORD
• 金额: $ 12.5万
• 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: 2006-07-01 至 2007-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7171648
• 关键词: NIH Roadmap Initiative tag; bioassay; cell line; chemical synthesis; hexosan; high throughput technology; inhibitor /antagonist; pentosan; small molecule; technology /technique development

DESCRIPTION (provided by applicant): Malignant transformation induces changes in the structures of many glycans. One of the most consistent alterations observed in a wide range of cancers is the increased expression of beta 1,6 branched N-linked glycans. Genetic experiments and human clinical data have shown that beta 1,6 branched N-linked glycans directly promote cancer progression. The goal of this proposal is to develop a cell-based screening system to identify inhibitors of the biosynthesis of complex beta 1,6 branched N-linked glycans. Small molecule inhibitors of the biosynthesis of beta 1,6 branched N-linked glycans will be useful as tools to study the biological roles of these glycans and as starting points to develop novel anti-cancer agents. Relevant structural changes in N-linked glycans have been shown to be associated with malignant transformation and metastasis. Specifically, an increase in beta 1,6 branched N-linked glycans in tumors has been found to promote aggressive cancer progression. The goal of this proposal is to develop a system to identify small molecule inhibitors of the biosynthesis of complex beta 1,6 branched N-linked glycans for the development as a novel anti-cancer drugs.

性状（由申请方提供）：恶性转化诱导许多聚糖的结构变化。 在广泛的癌症中观察到的最一致的改变之一是β 1，6分支N-连接聚糖的表达增加。 遗传实验和人类临床数据表明，β 1，6分支N-连接聚糖直接促进癌症进展。 该提案的目标是开发一种基于细胞的筛选系统，以鉴定复合β 1，6分支N-连接聚糖生物合成的抑制剂。 β 1，6分支N-连接聚糖生物合成的小分子抑制剂将可用作研究这些聚糖的生物学作用的工具，并作为开发新型抗癌剂的起点。 已显示N-连接聚糖的相关结构变化与恶性转化和转移相关。 具体而言，已发现肿瘤中β 1，6分支N-连接聚糖的增加促进侵袭性癌症进展。 本研究的目的是开发一种系统来鉴定复合β 1，6分支N-连接聚糖生物合成的小分子抑制剂，以开发为新型抗癌药物。