Kidney Multiphoton Analysis of Therapeutic Agents

描述(由申请人提供)：药物开发的速度令人失望地缓慢，部分原因是临床前药物研究未能阐明药物作用的机制。InPhoton已经证明，活体显微镜可以作为一种强大的工具用于临床前药物研究，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活体内肾脏毒性的定量显微镜分析方法，这是一种大量候选药物化合物的不良副作用。这些分析将在急性和慢性肾损伤的背景下使用公认的肾毒性模型来开发。该项目将导致开发独特的研究工具，这些工具可以用来补充和扩展传统的ADME-TOX方法，从而加快药物开发。这些工具将大大扩展InPhoton的能力和市场，为InPhoton的活体显微镜服务的大规模商业化迈出第一步，这最终将包括分析其他器官系统和体内肿瘤生物学的能力。 与公共健康相关：INPhoton，LLC将把活体肾脏显微镜商业化，作为一项合同研究服务，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处理和生理效应提供了独特的机械洞察力，从而加快了药物开发。

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.