NUCLEOSIDE ANALOGS AS ANTICANCER COMPOUNDS

总体目标是开发脱氧核苷类似物用于治疗 癌症患者。这包括对作用机制的研究。 和抵抗以及探索新的发展战略 具有独特性质的新核苷类似物。在此应用程序中，我们 将重点研究一种新型的L-核苷的抗肿瘤作用 类似物，L(-)二氧杂环胞苷(L(-)奇C)在本实验室发现。 这是基于研究部分的建议。具体目标是 列出： A.研究核苷转运抑制剂对摄取 L(-)奇C B.L(-)OddC的细胞内代谢研究 C.考察L(-)OddC及其代谢物与相关物质的相互作用 人体酵素 D.检测L(-)奇C对裸鼠肿瘤的抑制作用 小鼠模型 此外，我们将继续作为一个 共享公共关系的药物化学实验室资源 兴趣。这项拟议的研究应提供的信息不仅限于 新药发现的术语，还包括一些关于新药发现的基本知识 脱氧核苷的生化药理学。

The overall aim is to develop deoxynucleoside analogs for the treatment of patients with cancer. This includes the study of the mechanisms of action and resistance as well as the exploration of novel strategies to develop new nucleoside analogs with unique properties. In this application, we will focus on the study of the antitumor action of a novel L-nucleoside analog, L(-)dioxolane cytidine (L(-)OddC) discovered in this laboratory. This is based on the study section's recommendation. The Specific Aims are listed: A. Study the effect of nucleoside transport inhibitors on the uptake of L(-)OddC B. Study the intracellular metabolism of L(-)OddC C. Examine the interaction of L(-)OddC and its metabolites with relevant human enzymes D. Examine the antitumor activity of L(-)OddC against human tumor in nude mouse models In addition, we will continue to collaborate with and to serve as a resource to medicinal chemistry laboratories which share common related interests. This proposed study should provide information not only in terms of new drug discovery, but also some basic knowledge regarding the biochemical pharmacology of deoxynucleosides.