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"Discovery and Development of Anti-Diabetic Drugs."

“抗糖尿病药物的发现和开发。”

基本信息

批准号：
8058904
负责人：
GERARD M HOUSEY
金额：
$ 101.89万
依托单位：
HOUSEY PHARMACEUTICAL RESEARCH LAB
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8058904
关键词：
Antidiabetic Drugs Apoptosis Beta Cell Biological Biological Assay Biological Availability Boston Cell Survival Cell physiology Cells Chemical Agents Chemicals Development Diabetes Mellitus Disease Drug Design Drug usage Elements Eligibility Determination Epidemic Exhibits Experimental Diabetes Mellitus Foundations Funding Future Genes Genetic Polymorphism Goals Grant Growth Growth Factor Half-Life Health Homeostasis Human IRS2 gene In Vitro Insulin Insulin Resistance Insulin-Dependent Diabetes Mellitus Investigational Drugs Laboratories Laboratory Research Lead Licensing Mammalian Cell Marketing Mediating Michigan Molecular Mus Myeloid Progenitor Cells Non-Insulin-Dependent Diabetes Mellitus Nutrient Oral Pancreas Patients Pediatric Hospitals Peripheral Pharmaceutical Chemistry Pharmacologic Substance Phase Physiological Plasma Prevention Proteins Regulation Research Research Infrastructure Research Personnel Rodent Safety Scientist Signal Transduction Small Business Innovation Research Grant Specificity System Technology Testing Therapeutic Tissues United States United States National Institutes of Health Work base biological research cell growth commercialization direct application drug discovery effective therapy high throughput screening in vivo insulin secretion insulin sensitivity insulin signaling medical schools novel pre-clinical research study small molecule

项目摘要

DESCRIPTION (provided by applicant): This is a Resubmission of an NIH Phase II SBIR Renewal Application directed towards developing and optimizing compounds that are capable of stimulating IRS2 foundation for the treatment of Type II diabetes. If successful, such compounds may also be useful for the treatment of a subset of patients with Type I diabetes as well. The overall goal of this proposal is to engage in lead optimization studies of new molecular entities already identified by HPRL scientists that activate the IRS2-branch of the insulin signal transduction cascade in mammalian cells. The NIH SBIR funding support will be used to focus research at Housey Pharmaceutical Research Laboratories (hereinafter "HPRL") to further develop for future commercialization initial discoveries made in the laboratory of Dr. Morris White at the Children's Hospital of Boston, Harvard Medical School, and investigators at the Joslin Diabetes Center. These discoveries have been licensed to HPRL for therapeutic applications. Compounds that activate the IRS2-branch of the insulin-mediated signal transduction cascade have been identified by HPRL as a result of a high throughput screen (HTS) using a target-protein specific cell-based assay system. A subset of these compounds exhibit substantial ability to stimulate cell growth in an IRS2- specific manner. A selected group of such compounds will undergo testing in rodent and human 2-cells together with both in-vitro and in-vivo lead optimization studies in mice. Following successful completion of these studies, a small number of novel, lead-optimized new molecular entities should emerge which may be suitable for advancement into formal preclinical investigational new drug (IND) studies for the treatment of patients with Type II diabetes. 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 Phase II Renewal Grant mechanism provides the opportunity 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 disease of substantial proportions world-wide, pharmaceutical products and licensable technologies developed by HPRL will have substantial market opportunities. PUBLIC HEALTH RELEVANCE: Discovery and Development of Anti-Diabetic Drugs.

描述（由申请人提供）：这是NIH II期SBIR续期申请的重新提交，旨在开发和优化能够刺激IRS2基础的化合物，用于治疗II型糖尿病。如果成功，这些化合物也可能用于治疗一部分I型糖尿病患者。本提案的总体目标是参与HPRL科学家已经确定的激活哺乳动物细胞胰岛素信号转导级联的irs2分支的新分子实体的先导优化研究。NIH SBIR的资金支持将用于Housey制药研究实验室（以下简称“HPRL”）的重点研究，以进一步开发波士顿儿童医院、哈佛医学院的Morris White博士和乔斯林糖尿病中心的研究人员在实验室中进行的初步发现，以实现未来的商业化。这些发现已授权HPRL用于治疗应用。激活胰岛素介导的信号转导级联的irs2分支的化合物已经被HPRL鉴定为高通量筛选（HTS）的结果，使用靶向蛋白特异性细胞检测系统。这些化合物的一个子集表现出以IRS2特异性方式刺激细胞生长的实质性能力。一组选定的此类化合物将在啮齿动物和人类2细胞中进行测试，并在小鼠体内和体外进行铅优化研究。在成功完成这些研究之后，应该会出现少量新颖的、铅优化的新分子实体，它们可能适合推进正式的临床前研究新药（IND）研究，用于治疗II型糖尿病患者。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第二阶段续期拨款机制的支持，为利用HPRL的基础设施进行药物发现和设计前沿的新颖和创造性项目提供了机会。由于糖尿病是世界范围内占很大比例的主要疾病，HPRL开发的药品和许可技术将有大量的市场机会。