High Throughput Biology Core

高通量生物学核心

• 批准号: 10514149
• 负责人: Ujjini Havaldar Manjunatha
• 金额: $ 349.19万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-16 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10514149
• 关键词: Antiviral Agents; Archives; Area; Automation; Biochemical; Biological; Biological Assay; Biology; Cell Culture System; Cells; Chemicals; Collaborations; Coronavirus; Data; Data Management Resources; Development; Disease; Dose; Flavivirus; Funding; Generations; Goals; Guidelines; Henipavirus; In Vitro; Infrastructure; Knowledge; Lead; Libraries; Liquid substance; Machine Learning; Massachusetts; Medical; Miniaturization; Modeling; Molecular Target; Pathway interactions; Pharmaceutical Chemistry; Phenotype; Property; Proteins; Recombinant Proteins; Recombinants; Replicon; Reporter; Research; Resources; Robotics; Science; Site; Specificity; Structure-Activity Relationship; Switzerland; System; Testing; Texas; Universities; Validation; Viral; Viral Proteins; Virus; Work; assay development; base; clinical candidate; cohesion; cytotoxicity; data integrity; design; drug discovery; high throughput screening; improved; instrumentation; interest; lead candidate; lead optimization; miniaturize; novel; pandemic preparedness; protein expression; response; screening; small molecule libraries; tool; vector; virology

HIGH-THROUGHPUT BIOLOGY CORE – ABSTRACT The High-Throughput Biology Core will support Project Teams with target-based and phenotypic high-throughput screening (HTS) campaigns to identify diverse tractable chemical matter and SAR (structure-activity relationship)-enabling primary dose-response assays for lead identification and optimization efforts. This will be achieved in close collaboration with the Virology Core (providing molecular target hypothesis and develop BSL2 suitable vectors for translatable in vitro phenotypic assay systems) and the Drug Discovery Core (helping to design tailored screening sets for iterative HTS and providing medicinal chemistry support to enable lead identification and optimization). The High-Throughput Biology Core, with established in-house expertise in assay development and miniaturization, proficiency in diverse recombinant protein expression systems, compound and data management systems, and state-of-the-art screening and automation infrastructure including BSL2 HTS capability, will enable HTS to identify new chemical starting points for drug discovery and also validate new targets. Further, the High-Throughput Biology Core will also enable medicinal chemistry efforts to improve on-target potency and enhance selectivity with robust SAR-enabling primary dose-response assays. This will facilitate the optimization of lead candidates with improved physiochemical properties having desirable potency, selectivity and ADME properties to ultimately deliver safe and efficacious promising clinical candidates. In summary, the High-Throughput Biology Core will enable UNAPP’s drug discovery efforts by helping Project Teams to identify tractable diverse chemical matter necessary to validate new targets and support antiviral drug discovery to ultimately select the best candidate for development.

高通量生物学核心-摘要 高通量生物学核心将支持项目团队进行基于目标和表型的高通量 筛选（HTS）活动，以确定各种易处理的化学物质和SAR（结构-活性 关系）-使能用于铅识别和优化工作的主要剂量响应测定。这将是 与病毒学核心密切合作（提供分子靶点假设并开发BSL 2 用于可翻译的体外表型测定系统的合适载体）和药物发现核心（有助于 为迭代HTS设计定制的筛选集，并提供药物化学支持， 识别和优化）。高质量生物学核心，具有既定的内部专业知识， 分析开发和微型化，精通各种重组蛋白表达系统， 化合物和数据管理系统，以及最先进的筛选和自动化基础设施 包括BSL 2 HTS能力，将使HTS能够确定药物发现的新化学起点， 也验证新目标。此外，高通量生物学核心还将使药物化学 努力提高靶向效力并增强选择性，具有稳健的SAR使能主要剂量反应 测定。这将有助于优化具有改善的理化性质的先导候选物， 期望的效力、选择性和ADME性质，以最终提供安全有效的有前景的临床 候选人总之，高通量生物学核心将使UNAPP的药物发现工作 通过帮助项目团队确定验证新目标所需的易处理的多种化学物质， 并支持抗病毒药物的发现，以最终选择最佳候选药物进行开发。