Ultrahigh-throughput Identification of Molecular Targets of Natural Products

天然产物分子靶标的超高通量鉴定

• 批准号: 9263893
• 负责人: DAOJING WANG
• 金额: $ 81.13万
• 依托单位: NEWOMICS, INC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263893
• 关键词: Binding; Bioinformatics; Biological; Biological Assay; Biological Availability; Biomedical Research; Blood; Blood Cells; Blood specimen; Businesses; Cell Line; Clinical Research; Collaborations; Communities; Coupled; Crude Extracts; Databases; Development; Diabetes Mellitus; Diabetic mouse; Diagnosis; Disease Progression; Drug Kinetics; Foundations; Human; KRAS2 gene; Laboratories; Libraries; Liquid Chromatography; Malignant Neoplasms; Mass Spectrum Analysis; Microfluidic Microchips; Mississippi; Molecular Target; Monitor; Natural Products; Pathway interactions; Performance; Pharmaceutical Preparations; Phase; Plants; Preparation; Proteins; Proteome; Proteomics; Publishing; Reporting; Resveratrol; Sampling; Sensitivity and Specificity; Serum Albumin; Silicon; Small Business Innovation Research Grant; Source; Spectrometry, Mass, Electrospray Ionization; Technology; Therapeutic Effect; Tissues; Toxic effect; Universities; Validation; Vendor; Walkers; analog; base; commercialization; drug development; drug discovery; high throughput screening; in vivo; industry partner; innovation; insight; mass spectrometer; metabolome; metabolomics; mouse model; next generation; novel therapeutics; operation; public health relevance; research and development; response; screening; therapeutic evaluation; treatment response

 DESCRIPTION (provided by applicant): Natural products are rich sources for potential drugs. To accelerate drug discovery from natural products, it is imperative to identify their molecular targets, and mechanistically elucidate their bioavailability, toxicity, and therapeutic effects. However, there remain several challenges in the field. Among them, there is currently no technical platform that could perform mechanistic studies from the "hits" to "leads" using the small volumes of samples that are typically encountered in quantitative high-throughput screening or obtained from biological and clinical studies. To tackle these challenges and in response to RFA-AT-16-003, Newomics Inc. proposes to complete development of its product, a multiomics platform for high-throughput and high-content bioassays of natural products. The Phase II project is built upon the promising results generated from our Phase I project. In Phase I, we have developed ESI-MS assays to screen the interactions between molecular targets and natural products from libraries with different complexity. In Phase II, we will complete development of multiomics assays for commercialization, through working closely with industry partners, academic collaborators, and business consultants. Once developed, Newomics' Omics-chip may become a universal platform for high-throughput identification of molecular targets of natural products in the blood or other tissues, and lay a new foundation for drug discovery and development.

 描述（由申请人提供）：天然产品是潜在药物的丰富来源。为了加速从天然产物中发现药物，必须确定其分子靶点，并从机理上阐明其生物利用度，毒性和治疗效果。然而，在实地仍然存在若干挑战。其中，目前还没有技术平台可以使用定量高通量筛选中通常遇到的或从生物学和临床研究中获得的小体积样品进行从“命中”到“引线”的机制研究。为了应对这些挑战并响应RFA-AT-16-003，Newomics Inc.建议完成其产品的开发，这是一个多组学平台，用于高通量和高含量的天然产物生物测定。第二阶段项目建立在我们第一阶段项目产生的有希望的结果的基础上。在第一阶段，我们已经开发了ESI-MS分析，以筛选分子靶标与来自不同复杂性文库的天然产物之间的相互作用。在第二阶段，我们将通过与行业合作伙伴，学术合作者和商业顾问密切合作，完成商业化多组学检测的开发。一旦开发出来，Newomics的Omics-chip可能成为高通量鉴定血液或其他组织中天然产物分子靶标的通用平台，并为药物发现和开发奠定新的基础。