PHASE I TRIAL OF D1694, AN INHIBITOR OF THYMIDYLATE SYNTHASE

胸苷酸合酶抑制剂 D1694 的 I 期试验

• 批准号: 6246749
• 负责人: JAMES A WHITLOCK
• 金额: $ 3.1万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-27 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6246749
• 关键词: antineoplastics; child (0-11); clinical research; clinical trial phase I; dosage; drug screening /evaluation; enzyme inhibitors; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; pediatric neoplasm /cancer; pediatric pharmacology; pharmacokinetics; thymidylate synthase

This phase I study is designed to define the MTD (maximum tolerated dose) of D1694 in pediatric patients. Analogs of folic acid have been successfully used for the treatment of cancer for more than 40 years. The underlying mechanism of action for classial antifols such as methotrexate (MTX) is their ability to block the denovo synthesis of purine and pyrimidine nucleotide precursors of DNA, primarily by inhibiting dihydrofolate reductase (DHFR). Thymidylate synthase (TS), an enzyme which acts by utilizing 5, 10-CH2FH4 in the reductive methylation of deoxyuridylate (dUMP), is required for the de novo synthesis of thymidylate and is thus a potential target of folic acid analogs.

这项第一阶段研究旨在定义最大耐受量 D1694在儿科患者中的应用。叶酸的类似物已经被 成功用于癌症治疗已有40多年。 分类抗病毒药的基本作用机制如下 甲氨蝶呤(MTX)是指它们能够阻止甲氨蝶呤的从头合成。 DNA的嘌呤和嘧啶核苷酸前体，主要通过 抑制二氢叶酸还原酶(DHFR)。胸苷合成酶(TS)， 一种在还原过程中利用5，10-CH2FH4起作用的酶 脱氧尿苷(DUMP)的甲基化是从头合成所必需的 合成胸腺苷，因此是叶酸的潜在靶标 类比。