Medicinal Chemistry and Lead Development Core - EIDD

药物化学和先导化合物开发核心 - EIDD

• 批准号: 10580021
• 负责人: George Robert Painter
• 金额: $ 35.67万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-07 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580021
• 关键词: Animals; Antiviral Agents; Automobile Driving; Biological Assay; Chemistry; Data; Decision Making; Development; Excretory function; Generations; Goals; Human Resources; In Vitro; Individual; Lead; Metabolism; Microsomes; Pharmaceutical Chemistry; Pharmaceutical Preparations; Phase; Procedures; Process; Property; Research; Research Project Grants; Role; Site; Solubility; Structure-Activity Relationship; Synthesis Chemistry; Testing; Therapeutic; Translational Research; Work; absorption; analog; data management; design; drug development; drug discovery; drug-like compound; emerging pathogen; experimental study; in vivo; inhibitor; lead candidate; lead optimization; new chemical entity; novel; process optimization; programs; structural biology; translational research program

The Medicinal Chemistry and Lead Development Core (MCLDC) is a key component of the Antiviral Drug Discovery and Development Center (AD3C) that will contribute to the goals of the overall Center of Excellence for Translational Research (CETR) program to develop new replication inhibitors and other broad-based therapeutics for the treatment of emerging pathogens through its interaction with each of the individual projects and cores. The MCLDC will provide a) synthetic chemistry, b) structure-activity relationship (SAR) data and analysis, c) lead optimization chemistry, d) bioanalytical assays, e) structural biology and computational support, and d) compound storage and data management. In this role, the MCLDC, in conjunction with the Assay Core, will be the central focus of the translational research component of the program. As such, the MCLDC will work closely with the Assay Core and each of the Research Project teams. As new chemical entities are designed and synthesized during the lead generation and optimization processes, the Assay Core will test these analogs in SAR-driving assays. Testing of compounds for drug-like properties such as microsomal stability and solubility; and in vitro Absorption, Distribution, Metabolism and Excretion (ADME) will be an integral part of SAR studies from the early developmental phase. Appropriate lead compounds will be provided to the various Research Project teams for advanced studies including efficacy, mechanism of action, and other experiments. The resulting data on lead compounds from the Assay Core and Research Projects will then be analyzed by the MCLDC to drive the iterative lead optimization and in vivo PK studies to completion, resulting in optimized leads with drug-like properties for animal studies. The lead candidates will have met the go/no go decision criteria set for activity, potency and drug-like properties. The goal for the end result of this process will be identification of novel optimized lead molecules that are appropriate for IND applications. The MCLDC will incorporate key personnel of other Cores and Research Project teams into the prioritization and decision–making procedures.

药物化学和铅发育核心（MCLDC）是抗病毒药物的关键组成部分 发现与发展中心（AD3C）将有助于整个卓越中心的目标 用于转化研究（CERT）计划，以开发新的复制抑制剂和其他基于广泛的抑制剂 通过与每个项目的互动来治疗新兴病原体的治疗剂 和核心。 MCLDC将提供a）综合化学，b）结构活性关系（SAR）数据和 分析，c）铅优化化学，d）生物分析测定，e）结构生物学和计算支持， d）复合存储和数据管理。在这个角色中，MCLDC与测定核心一起 将是该计划的转化研究组成部分的主要重点。因此，MCLDC将工作 与测定核心和每个研究项目团队紧密相关。由于设计了新的化学实体 并在潜在客户生成和优化过程中合成，测定核心将测试这些类似物 在SAR-Driver测定中。测试化合物的类似药物样特性，例如微粒体稳定性和可溶性； 体外吸收，分布，代谢和排泄（ADME）将是SAR研究的组成部分 从早期发育阶段。各种研究将提供适当的铅化合物 高级研究的项目团队，包括效率，行动机理和其他实验。这 然后，从分析核心和研究项目的铅化合物中产生的数据将由 MCLDC推动迭代铅优化和体内PK研究完成，从而获得优化的潜在客户 具有用于动物研究的药物样特性。主要候选人将满足GO/NO DE决策标准 用于活动，效力和类似药物的特性。此过程的最终结果的目标将是确定 适用于IND应用的新型优化铅分子。 MCLDC将合并钥匙 其他核心和研究项目团队的人员进行了优先级和决策程序。