Discovery and development of Antidiabetic Drugs

描述(由申请人提供)：这项名为“抗糖尿病药物的发现和开发”的第一阶段SBIR申请建议建立检测系统，以识别和验证促进哺乳动物细胞中胰岛素受体底物2(IRS2)功能的小分子。IRS2介导胰岛素和胰岛素样生长因子受体在调节营养动态平衡的生物过程中的作用。胰岛素作用的失调会导致糖尿病，这是一种日益令人担忧的疾病，目前仅在美国就有1600多万人受到影响。过去几年进行的基础科学研究表明，IRS2是外周胰岛素作用和胰岛β细胞胰岛素产生的重要元件。由于糖尿病患者的胰岛素分泌和作用失效，合理发现和设计增强IRS2功能的小分子可能会从根本上改善糖尿病的治疗和最终治愈。这项第一阶段的SBIR应用旨在发现能够激活细胞中人类IRS2蛋白的化学试剂。目前，在本申请中提出的药物类别中，没有已知的化合物被批准用于临床使用(即IRS2靶蛋白的激活剂)，目前甚至没有已知的临床前试验中存在的化合物。因此，这一领域的成功将创造一种全新的治疗剂，用于糖尿病治疗的临床应用。SBIR资金将用于建立和验证基于细胞的分析，以确定促进IRS2信号转导的小分子实体。在Moroever，SBIR的支持将部分用于留住杰出的化学和生物科学家，在该公司位于密歇根州的实验室实施这一计划。HPRL是一个功能齐全的化学和生物研究实验室，配备了现代分子和细胞生物学研究，包括高通量筛选。通过SBIR机制的支持为利用HPRL的基础设施在药物发现和设计的前沿进行新颖和创造性的项目提供了机会。由于糖尿病是一种流行性的主要慢性疾病，由HPRL开发的药品将在全球范围内拥有巨大的市场机会。

DESCRIPTION (provided by applicant): This Phase I SBIR application entitled "Discovery and Development of Antidiabetic Drugs," proposes to establish assay systems to identify and validate small molecules that promote the function of the insulin receptor substrate 2 (IRS2) in mammalian cells. IRS2 mediates the action of insulin and insulin-like growth factor receptors upon biological processes that regulate nutrient homeostasis. Dysregulation of insulin action results in diabetes, a disease of growing concern that currently afflicts more than 16 million people in the United States alone. Basic scientific investigation conducted over the past several years reveals that IRS2 is an essential element in both peripheral insulin action and pancreatic beta cell insulin production. Since insulin secretion and action fail in people with diabetes, the rational discovery and design of small molecules that enhance the function of IRS2 might lead to fundamental improvements in the treatment and eventual cure of diabetes. This Phase I SBIR application is directed toward the discovery of chemical agents capable of activating the human IRS2 protein in cells. At the present time there are no known compounds approved for clinical use in the drug class which is being proposed in this application (namely activators of the IRS2 target protein), and none are even known to exist in pre-clinical testing at the present time. Therefore, success in this area will create an entirely new class of therapeutic agent for clinical applications to diabetes care. The SBIR funds will be used to establish and validate cell-based assays to identify small molecular entities that promote IRS2 signaling. Moroever, SBIR support will be used in part to retain outstanding chemical and biological scientists to conduct this program at the Company's laboratories in Michigan HPRL is a fully functional chemical and biological research laboratory that is equipped for modern molecular and cell biological studies, including high throughput screening. Support through the SBIR mechanism provides the opportunitiy to utilize the infrastructure at HPRL for novel and creative projects at the cutting edge of drug discovery and design. Since diabetes is a major chronic disease of epidemic proportions, pharmaceutical products developed by at HPRL will have large market opportunities world-wide.