Kidney Multiphoton Analysis of Therapeutic Agents

治疗药物的肾脏多光子分析

• 批准号: 8120810
• 负责人: KENNETH W DUNN
• 金额: $ 41.87万
• 依托单位: INPHOTON, LLC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8120810
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Address; Adverse effects; American; Animals; Apoptotic; Biological Assay; Biotechnology; Blood Vessels; Businesses; Cell Death; Cell physiology; Cells; Chronic; Chronic Kidney Failure; Chronology; Client; Complement; Contrast Media; Cultured Cells; Custom; Data; Detection; Development; Diabetic Nephropathy; Diatrizoate Sodium; Drops; Drug Compounding; Drug Delivery Systems; Drug Industry; Drug Transport; Drug effect disorder; Drug toxicity; Event; Failure; Fibrosis; Gentamicins; Injury; Ischemia; Kidney; Kidney Diseases; Lipopolysaccharides; Longitudinal Studies; Marketing; Measures; Metabolism; Methods; Microvascular Permeability; Modeling; Nature; Necrosis; Patients; Pharmaceutical Preparations; Phase; Physiological; Physiology; Positioning Attribute; Preclinical Drug Development; Predisposition; Process; Radio; Renal function; Research; Research Contracts; Resolution; Sampling; Services; Streptozocin; Structure; Therapeutic Agents; Toxic effect; Toxicology; Toxin; Tubular formation; Tumor Biology; base; body system; commercialization; cost effective; design; drug candidate; drug development; drug distribution; experience; in vivo; indexing; insight; intravital microscopy; novel; pre-clinical; preclinical study; public health relevance; renal artery; tool; uptake

DESCRIPTION (provided by applicant): The rate of drug development is disappointingly slow, in part because of the failure of preclinical drug studies to elucidate the mechanisms of drug actions. INphoton has demonstrated that intravital microscopy can be used as a powerful tool in preclinical drug studies, providing the mechanistic insights typically associated with studies of cultured cells, but in the physiologically relevant context of the intact animal. Here we propose to develop an integrated set of quantitative intravital microscopy assays of renal toxicity, an undesired side-effect of a large number of candidate drug compounds. These assays will be developed using well-established models of renal toxicity in the context of both acute and chronic renal injury. This project will result in the development of unique research tools that can be used to complement and extend traditional ADME-tox approaches in ways that will expedite drug development. These tools will significantly extend INphoton's capabilities and market, providing the first step in the wide-scale commercialization of INphoton's intravital microscopy services, which will ultimately include capabilities for analyses of other organ systems and of in vivo tumor biology. PUBLIC HEALTH RELEVANCE: INphoton, LLC will commercialize intravital microscopy of the kidney as a contract research service to be used as an investigational tool for preclinical drug development. The high resolution provided by this approach provides unique mechanistic insights into the cellular processing and physiological effects of candidate drug compounds, thereby expediting drug development.

描述（由申请人提供）：药物开发的速度非常缓慢，部分原因是临床前药物研究未能阐明药物作用机制。INphoton已经证明，活体显微镜可用作临床前药物研究的有力工具，提供通常与培养细胞研究相关的机制见解，但在完整动物的生理相关背景下。在这里，我们建议开发一套完整的定量肾毒性活体显微镜检测，一个不希望的副作用，大量的候选药物化合物。将在急性和慢性肾损伤的背景下使用成熟的肾毒性模型开发这些试验。该项目将导致开发独特的研究工具，可用于补充和扩展传统的ADME毒性方法，以加快药物开发。这些工具将大大扩展INphoton的能力和市场，为INphoton活体显微镜服务的大规模商业化迈出了第一步，最终将包括其他器官系统和体内肿瘤生物学的分析能力。 公共卫生相关性：INphoton，LLC将把肾脏活体显微镜作为合同研究服务商业化，作为临床前药物开发的研究工具。这种方法提供的高分辨率为候选药物化合物的细胞加工和生理作用提供了独特的机制见解，从而加快了药物开发。