DEVELOPMENT OF CHEMOPREVENTIVE RETINOIDS

化学预防性维A酸的开发

• 批准号: 3093597
• 负责人: Donald L. Hill
• 金额: $ 105.84万
• 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 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3093597
• 关键词: cancer prevention; carcinogenesis inhibitor; chemical synthesis; drug design /synthesis /production; drug metabolism; 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.

这个全面的程序用于设计，合成和 评估新的类维生素类动物作为潜在的化学预防剂。 从所有准备的类视黄素中选择最大的类维生素 化学预防电位，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 选定的将在体内测试它们在防止皮肤方面的作用 乳头状瘤，膀胱癌和乳腺癌。 为了 其中一个或多个具有相当大活动的化合物 系统，药理和毒理学研究将是 执行。 这些研究的结果，对 结构活动关系将用于指导 新化合物设计中的合成程序并选择 候选人进行临床研究。 研究项目，每个项目都与行动机理有关 类视网膜类似，关注（a）与结合和结合相关的早期事件 摄取类视黄素和肿瘤促进； （b）功能 视黄酸结合蛋白； （c） 类视黄素的性格和化学预防活性； （D） 评估类视网膜生物对免疫功能的影响； （e） 具有潜在化学预防的新类维生素类似的合成 活动，但毒性很少。 新的，更有效且毒性较小的性类维生素的发展 会给那些或将来的人提供治疗的希望 暴露于大量的致癌物和他人 确定有癌症的高风险。