Botannical Extract Library Screeninig with Human ADAS Cells

使用人类 ADAS 细胞筛选植物提取物文库

• 批准号: 7478265
• 负责人: Jeffrey Martin Gimble
• 金额: $ 22.9万
• 依托单位: ZEN-BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478265
• 关键词: Abbreviations; Adipocytes; Adipose tissue; Adult; Antigens; Basic Science; Biological Assay; Biomedical Research; Body mass index; Botanicals; Butyric Acid; Butyric Acids; Cardiovascular Diseases; Cell Line; Cell model; Cells; Chemicals; Collaborations; Complement 2; Development; Diabetes Mellitus; Diabetic Diet; Diagnostic; Dimethyl Sulfoxide; Fatty Acids; Fatty acid glycerol esters; Fractionation; Funding; Gene Expression; Gene Expression Profiling; Glial Fibrillary Acidic Protein; Goals; Heart; Histocompatibility; Histocompatibility Testing; Human; Human Genome; Income; Institution; Intellectual Property; Lead; Libraries; Licensing; Lipolysis; Mesenchymal Stem Cells; Metabolic syndrome; Methods; Microtubule-Associated Protein 2; Modeling; Morphologic artifacts; Mus; National Cancer Institute; Nicotinic Acids; Obesity; Outcome; Patients; Peripheral; Peroxisome Proliferator-Activated Receptors; Personal Satisfaction; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plant Extracts; Positioning Attribute; Prevention; Proteins; Public Health; Reagent; Research; Research Institute; Research Personnel; Scientist; Screening procedure; Serum; Services; Small Business Technology Transfer Research; Stem cells; Study Section; Suggestion; System; TNF gene; Talents; Technical Expertise; Testing; Therapeutic Effect; Translational Research; Translations; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States National Institutes of Health; Universities; Work; Writing; base; cardiovascular risk factor; combinatorial; cytotoxic; diabetic; drug development; fetal; gamma-Aminobutyric Acid; high throughput screening; human TNF protein; improved; lipid biosynthesis; novel; obesity treatment; response; small molecule libraries; stem; telomerase reverse transcriptase; tool

DESCRIPTION (provided by applicant): This Phase I STTR proposal has been substantially revised in response to the Study Section review. The proposal was written in response to the NIH Director's newly released }roadmap} that encourages collaboration between corporate and academic institutions to develop alternative models for conducting research and the suggestion by Dr. Francis Collins, Director of the National Human Genome Research Institute, that }academic pursuit of [the] first step in drug development could be particularly valuable}. This STTR Phase I proposal combines the talents of Zen-Bio, Inc., the leading commercial supplier of human adipose tissue-derived cells for pharmaceutical research, with those of an NIH-funded Botanical Research Center at the Pennington Biomedical Research Center, an internationally recognized center for studies of diabetes and nutrition, and Rutgers University, an internationally recognized center for the development of botanical extracts. Our overarching hypothesis is that botanicals may effect one or more tissue types in the development of metabolic syndrome and extracts that limit the amount of fatty acid }release} in adipose tissue (lipolysis or TG accumulation) will reduce the amount of ectopic peripheral fat accumulation and cardiovascular risk (e.g. niacin). In the Phase I proposal, we hypothesize that high-throughput screening assays using human adipose cell models will: (1) Identify novel lead compounds from an existing botanical library and; (2) Complement existing assays in the fractionation of extracts from botanicals with known benefits for obese, diabetic, or hypertensive patients. As the commercial partner, Zen-Bio brings an existing portfolio of high-throughput human cell-based assays for lipogenesis, lipolysis, and adipogenic gene expression profiling. As the academic partner, the Botanical Center at PBRC in collaboration with Rutgers University provides its unique library of botanical extracts and chemical fractionation expertise. In addition, the Botanical Center has already subfractionated botanical extracts from plants with identified therapeutic effects for cardiovascular disease, diabetes, and obesity. All of these tools and reagents will be available for the proposed studies. Prior studies validate the utility and efficacy of this approach. The murine 3T3-L1 pre-adipocyte cell line has been used to screen a combinatorial chemical library for lead compounds promoting or inhibiting adipogenesis (2); however, it is well known that compounds identified in murine models often fail as human pharmacological agents. PUBLIC HEALTH RELEVANCE: The chemicals identified through this STTR may have potential application in the treatment of obesity, diabetes, and metabolic syndrome. The outcome of this work will have direct commercial implications for both Zen-Bio and the Pennington Biomedical Research Center in terms of potential products, licensing opportunities, and intellectual property.

描述（由申请人提供）：根据研究章节的审查，对本I期STTR提案进行了实质性修订。该提案是为了响应NIH主任最新发布的路线图，该路线图鼓励企业和学术机构合作开发进行研究的替代模型，以及国家人类基因组研究所所长弗朗西斯柯林斯博士的建议，即}药物开发第一步的学术追求可能特别有价值}。这个STTR第一阶段的建议结合了Zen-Bio公司的人才，作为用于药物研究的人类脂肪组织衍生细胞的领先商业供应商，美国国立卫生研究院资助的彭宁顿生物医学研究中心的植物研究中心，国际公认的糖尿病和营养研究中心，以及罗格斯大学，国际公认的植物提取物开发中心。我们的首要假设是，植物药可能会影响代谢综合征发展中的一种或多种组织类型，并且限制脂肪组织中脂肪酸释放量（脂肪分解或TG积累）的提取物将减少异位外周脂肪积累的量和心血管风险（例如尼克酸）。在第一阶段的提案中，我们假设使用人类脂肪细胞模型的高通量筛选试验将：（1）从现有的植物库中识别新的先导化合物;（2）补充现有的植物提取物分级分离试验，对肥胖，糖尿病或高血压患者具有已知的益处。作为商业合作伙伴，Zen-Bio带来了现有的高通量人类细胞检测产品组合，用于脂肪生成，脂解和脂肪生成基因表达谱。作为学术合作伙伴，PBRC植物中心与罗格斯大学合作，提供其独特的植物提取物和化学分馏专业知识库。此外，植物中心已经对植物提取物进行了细分，这些植物提取物对心血管疾病、糖尿病和肥胖症具有确定的治疗作用。所有这些工具和试剂将可用于拟定研究。先前的研究验证了这种方法的实用性和有效性。鼠3 T3-L1前脂肪细胞系已用于筛选促进或抑制脂肪生成的先导化合物的组合化学文库（2）;然而，众所周知，在鼠模型中鉴定的化合物通常不能作为人类药理学试剂。公共卫生相关性：通过该STTR鉴定的化学物质可能在治疗肥胖、糖尿病和代谢综合征方面具有潜在的应用。这项工作的结果将对Zen-Bio和彭宁顿生物医学研究中心在潜在产品、许可机会和知识产权方面产生直接的商业影响。