DEVELOPMENT OF CHEMOPREVENTIVE RETINOIDS

化学预防性维A酸的开发

• 批准号: 3093605
• 负责人: Donald L. Hill
• 金额: $ 116.78万
• 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 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3093605
• 关键词: carcinogenesis inhibitor; chemical synthesis; chemoprevention; nutrition related tag; retinoids

This comprehensive program is for the design, synthesis, and evaluation of new retinoids as potential chemopreventive agents. To select retinoids with the greatest potential, the compounds are evaluated initially in biochemical systems and in systems designed to measure their effect in enhancing immunological responses. Those selected, on the basis of high activity in these tests, are evaluated, as appropriate, in intact animals for their effect in preventing skin papillomas, Moloney virus-induced lymphomas, and/or mammary carcinomas. For compounds having substantial activity in one or more of these systems, pharmacological and toxicological studies are performed. Results of these studies, with observations on the structure-activity relationships, are used to guide the synthesis program in the design of new compounds and to select candidates for clinical investigation. Development of new, less toxic retinoids offers potential therapy to individuals who are at high risk for developing cancer. Research projects concern (a) synthesis of new conformationally restricted retinoids with potential biological activity; (b) evaluation of the effects of retinoids on immune function; and (c) synthesis of new retinoids related in structure to those with known chemopreventive activity and little toxicity. The core components deal with (a) preparation of large amounts of retinoids for biological evaluation, (b) evaluation in mice of compounds designed to prevent skin cancer, (c) the pharmacological and toxicological properties of retinoids, (d) evaluation in rats of compounds designed to prevent mammary cancer, (e) the binding of retinoids to various binding proteins and receptors, and (f) statistical evaluation and program administration. Developmental and interactive research is conducted in both the research projects and core components.

这个综合计划是用于设计，合成和评估 新的类视黄素作为潜在的化学预防剂。 选择类类类动物 具有最大的潜力，最初评估化合物 生化系统和旨在衡量其影响的系统 增强免疫学反应。 选择的那些，基于高 在这些测试中的活性在完整动物中进行了适当的评估 为了防止皮肤乳头状瘤的作用，莫洛尼病毒诱导 淋巴瘤和/或乳腺癌。 对于具有实质性的化合物 这些系统中的一个或多个，药理和毒理学的活动 进行研究。 这些研究的结果，对 结构活性关系用于指导综合程序 在设计新化合物并选择临床候选人中 调查。 开发新的，毒性较小的类维生素类似的潜力 对患癌症高风险的个体进行治疗。 研究项目关注（a）合成新构象限制的 具有潜在生物学活性的视网膜类似； （b）评估效果 维生素的免疫功能； （c）合成新的类维生素相关的合成 对于已知化学预防活性和很少的人的结构 毒性。 核心组件涉及（a）大量准备 类维生素的生物学评估，（b）化合物小鼠的评估 （c）药理和毒理学旨在预防皮肤癌 类维生素类似的特性，（d）评估旨在的化合物的大鼠 预防乳腺癌，（e）类维生素素与各种结合的结合 蛋白质和受体，以及（f）统计评估和程序 行政。 发展和互动研究是在 研究项目和核心组成部分。