High Throughput Biology Core

高通量生物学核心

• 批准号: 10845858
• 负责人: Ujjini Havaldar Manjunatha
• 金额: $ 59.98万
• 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/10845858
• 关键词: Antiviral Agents; Archives; Area; Automation; Biochemical; Biological; Biological Assay; Biology; Cell Culture System; Cells; Chemicals; Collaborations; Coronavirus; Data; Data Management Resources; Dedications; Development; Disease; Dose; Enabling Factors; 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; clinical candidate; 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.

高通量生物核心——摘要 高通量生物学核心将为项目团队提供基于目标和表型的高通量支持 筛选 (HTS) 活动，以识别多种易处理的化学物质和 SAR（结构-活性 关系）-启用主要剂量反应测定以进行先导物识别和优化工作。这将是 与病毒学核心密切合作实现（提供分子靶点假设并开发 BSL2 适用于可翻译体外表型测定系统的载体）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以实现领先 识别和优化）。高通量生物学核心，在以下方面拥有成熟的内部专业知识 检测开发和小型化，熟练掌握多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 BSL2 HTS 能力，将使 HTS 能够确定药物发现的新化学起点， 还验证新目标。此外，高通量生物学核心还将使药物化学成为可能 努力通过强大的SAR启用主要剂量反应来提高靶向效力并增强选择性 化验。这将有助于优化具有改善的理化性质的先导候选物 理想的效力、选择性和 ADME 特性，最终提供安全有效、有前景的临床药物 候选人。总之，高通量生物学核心将使 UNAPP 的药物发现工作成为可能 通过帮助项目团队识别验证新目标所需的可处理的不同化学物质 支持抗病毒药物的发现，最终选择最佳的候选药物进行开发。