DEVELOPMENT OF CHEMOPREVENTIVE RETINOIDS

化学预防性维A酸的开发

• 批准号: 3093604
• 负责人: Donald L. Hill
• 金额: $ 107.31万
• 依托单位: SOUTHERN RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3093604
• 关键词: cancer prevention; carcinogenesis inhibitor; chemical synthesis; nutrition related tag

This comprehensive program is for the design, synthesis, and evaluation of new retinoids as potential chemopreventive agents. To select, from all that are prepared, retinoids with the greatest chemopreventive potential, the compounds will be evaluated initially in biochemical and organ culture systems and in systems designed to measure their immunological properties. Those selected will be tested in vivo for their effect in preventing skin papillomas, bladder cancer, and mammary carcinomas. For compounds having considerable activity in one or more of these systems, pharmacological and toxicological studies will be performed. The results of these studies, with observations on the structure-activity relationships, will be used to guide the synthesis program in the design of new compounds and to select candidates for clinical investigation. Research projects, each relating to the mechanism of action of retinoids, concern (a) early events associated with the binding and uptake of retinoids and with tumor promotion; (b) the function of retinoic acid binding proteins; (c) the relationship between disposition and chemopreventive activity of retinoids; (d) evaluation of the effects of retinoids on immune function; and (e) synthesis of new retinoids having potential chemopreventive activity, but little toxicity. The development of new, more effective, and less toxic retinoids would offer hope of therapy to those who have been or will be exposed to substantial quantities of carcinogens and to others determined to be at high risk for cancer.

这个综合程序用于设计、合成和 评估新的类维生素A作为潜在的化学预防剂。 从所有准备好的类视黄醇中选择具有最大 化学预防潜力，将评估化合物 最初在生化和器官培养系统以及系统中 旨在测量其免疫学特性。 那些 选定的产品将在体内测试其预防皮肤病的效果 乳头状瘤、膀胱癌和乳腺癌。 为了 在这些中的一种或多种中具有显着活性的化合物 系统、药理学和毒理学研究将 执行。 这些研究的结果以及对 结构-活性关系，将用于指导 新化合物设计和选择的合成程序 临床研究的候选人。 研究项目，每个都与作用机制有关 类维生素A，关注（a）与结合相关的早期事件和 类视黄醇的摄取和肿瘤促进作用； (b) 的功能 视黄酸结合蛋白； (c) 之间的关系 类维生素A的处置和化学预防活性； (四) 评估类维生素A对免疫功能的影响；和(e) 具有潜在化学预防作用的新类维生素A的合成 活性高，但毒性小。 开发新的、更有效、毒性更小的维A酸 将为那些已经或将要接受治疗的人带来治疗的希望 接触大量致癌物质和其他物质 确定患有癌症的高风险。