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In Vivo Zebrafish Tyrosine Kinase ELISA

体内斑马鱼酪氨酸激酶 ELISA

基本信息

批准号：
7540337
负责人：
Chunqi Li
金额：
$ 20.14万
依托单位：
PHYLONIX PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-26 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7540337
关键词：
Amino Acid Sequence Animal Model Animals Antibodies Arthritis Attention Biological Assay Cardiovascular Diseases Cells Complex Data Development Diabetes Mellitus Disease Dose Drug Delivery Systems Drug Receptors Embryo Environment Enzyme-Linked Immunosorbent Assay Enzymes Erlotinib Evaluation Exhibits Family Fertilization G-Protein-Coupled Receptors Gefitinib Genes Genetic Gleevec Government Hour Human In Situ Hybridization Maintenance Malignant Neoplasms Mammals Mitogen-Activated Protein Kinase 3 Numbers Peptide Sequence Determination Persons Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Physiological Pilot Projects Preclinical Drug Evaluation Procedures Protein Kinase Protein Tyrosine Kinase Proteins Public Health Purpose Pyrimidine Pyrimidines Research Serine Somites Staging Staining method Stains Standards of Weights and Measures Statistically Significant Testing Therapeutic Threonine Time Tyrosine Tyrosine Kinase Inhibitor Yolk Sac Zebrafish base cost drug discovery human BCAR1 protein in vivo inhibitor/antagonist inorganic phosphate kinase inhibitor member research study small molecule src-Family Kinases success

项目摘要

DESCRIPTION (provided by applicant): The recent success of small-molecule ATP-competitive kinase inhibitors such as Gleevec, Iressa, and Tarceva has attracted significant attention and protein kinases now represent one of the most important groups of targets for drug discovery and development. Because of their genetic and physiological similarity to humans, zebrafish show promise as an efficient animal model for drug screening. Although all members of the mammalian protein kinases have not yet been identified in zebrafish, in situ hybridization experiments showed that Src family of tyrosine kinases src, fyn and yes are ubiquitously expressed in zebrafish embryos. In this research, we will develop a high throughput in vivo zebrafish ELISA format for identifying Src family kinase inhibitors. The zebrafish assay permits evaluation of the therapeutic potential of a compound in a complex physiological environment using throughput similar to cell-based assays. Advantages of the zebrafish assay include: short assay time, low cost, ease of embryo maintenance during drug delivery, compatibility of assay procedures with standard microplate formats, single drug dosing for each embryo, and the ability to test large numbers of embryos for statistically significant results. PUBLIC HEALTH RELEVANCE: In this research, we will develop a high throughput in vivo zebrafish ELISA format for identifying Src family kinase inhibitors.

描述（由申请人提供）：小分子 ATP 竞争性激酶抑制剂（例如格列卫、易瑞沙和特罗凯）最近的成功引起了人们的广泛关注，蛋白激酶现在代表了药物发现和开发的最重要的靶标组之一。由于斑马鱼与人类的遗传和生理相似性，因此有望成为药物筛选的有效动物模型。尽管尚未在斑马鱼中鉴定出哺乳动物蛋白激酶的所有成员，但原位杂交实验表明，酪氨酸激酶Src家族的src、fyn和yes在斑马鱼胚胎中普遍表达。在这项研究中，我们将开发一种高通量体内斑马鱼 ELISA 格式，用于鉴定 Src 家族激酶抑制剂。斑马鱼测定允许使用类似于基于细胞的测定的通量来评估化合物在复杂生理环境中的治疗潜力。斑马鱼测定的优点包括：测定时间短、成本低、药物输送过程中易于胚胎维护、测定程序与标准微孔板格式的兼容性、每个胚胎的单一药物剂量以及测试大量胚胎以获得统计显着结果的能力。公共健康相关性：在这项研究中，我们将开发一种高通量体内斑马鱼 ELISA 格式，用于鉴定 Src 家族激酶抑制剂。