Assay for Determining Drug Toxicity

药物毒性测定方法

• 批准号: 6660676
• 负责人: Chuenlei Parng
• 金额: $ 36.36万
• 依托单位: PHYLONIX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-11 至 2005-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6660676
• 关键词: bioassay; biological models; cisplatin; cyclophosphamide; drug screening /evaluation; embryo /fetus drug adverse effect; embryo /fetus pharmacology; gene expression; in situ hybridization; model design /development; molecular cloning; neoplasm /cancer pharmacology; pharmacokinetics; teratogens; zebrafish

DESCRIPTION (provided by applicant): Preclinical testing requires performance of laboratory and animal studies to determine the biological activity of the drug candidate against the targeted disease as well as drug safety. These tests take at least three years in mammalian models and only a very small number of compounds proceed to human testing. The cell culture system is currently used as an in vivo assay to evaluate molecular and regulatory effects within cells for drug discovery, however, cells lacking intact metabolic machinery often experience fewer toxic effects compared to animal models. This SBIR aims to develop the zebrafish as an inexpensive animal model for drug toxicity testing. Using zebrafish embryos, this SBIR will develop a comprehensive toxicity prescreening system comprised of a low density array and complementary visual assays to examine gene expression, cellular damage and morphological defects in response to drug treatment. The proposed zebrafish assays will help to reduce drug development costs by reducing the number of compounds entering preclinical mammalian and human testing. PROPOSED COMMERCIAL APPLICATION: By providing a rapid and inexpensive toxicity prescreening system, the zebrafish assays will facilitate the drug development process for a variety of diseases, including cancer and heart disease.

描述（由申请人提供）：临床前测试需要实验室和动物研究的性能，以确定候选药物针对靶向疾病以及药物安全的生物学活性。这些测试在哺乳动物模型中至少需要三年，只有很少的化合物进行人体测试。目前，细胞培养系统被用作评估细胞内分子和调节作用的体内测定，但是，与动物模型相比，缺乏完整代谢机械的细胞通常会造成更少的毒性作用。该SBIR旨在发展斑马鱼作为药物毒性测试的廉价动物模型。使用斑马鱼胚胎，该SBIR将形成一个全面的毒性预筛查系统，该系统由低密度阵列和互补视觉测定法组成，以检查基因表达，细胞损伤和形态缺陷，以应对药物治疗。拟议的斑马鱼测定法将通过减少进入临床前哺乳动物和人类测试的化合物的数量来帮助降低药物开发成本。 拟议的商业应用：通过提供快速且廉价的毒性预筛查系统，斑马鱼测定法将促进各种疾病的药物开发过程，包括癌症和心脏病。