NUCLEOSIDE ANALOGS AS ANTICANCER COMPOUNDS

总体目标是开发用于治疗以下疾病的脱氧核苷类似物： 癌症患者。 这包括研究作用机制 以及探索新的发展战略 具有独特性质的新型核苷类似物。在本申请中，我们 将重点研究一种新的L-核苷的抗肿瘤作用 类似物，L（-）二氧戊环胞苷（L（-）OddC）。 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（-）OddC B。L（-）OddC的细胞内代谢研究 C.检查L（-）OddC及其代谢产物与相关药物的相互作用。 人类酶 D.检测L（-）OddC对裸鼠人肿瘤的抗肿瘤活性 小鼠模型 此外，我们将继续与 药物化学实验室的资源， 利益这项拟议的研究不仅应提供信息， 新药发现方面，但也有一些基本知识， 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.