Medicinal Chemistry and Lead Development Core - SR

药物化学和先导开发核心(MCLDC)是抗病毒药物的关键组成部分 发现和开发中心(AD3C)，这将有助于实现卓越中心的整体目标 用于翻译研究(CETR)计划，以开发新的复制抑制剂和其他广泛的 通过与每个单独项目的互动来治疗新出现的病原体的治疗学 和核心。MCLDC将提供a)合成化学，b)结构-活性关系(SAR)数据和 分析，c)优化化学，d)生物分析，e)结构生物学和计算支持， 和d)复合存储和数据管理。在这一角色中，MCLDC与检测核心一起， 将是该方案翻译研究部分的中心重点。因此，MCLDC将发挥作用 与分析核心和每个研究项目团队密切合作。随着新的化学物质被设计出来 并在引线生成和优化过程中进行合成，Assay Core将测试这些类似物 在搜救驾驶测试中。测试化合物的类药物特性，如微粒体稳定性和溶解性； 体外吸收、分布、代谢和排泄(ADME)将是SAR研究的组成部分 从早期发育阶段开始。适当的先导化合物将被提供给各种研究 项目团队进行高级研究，包括疗效、作用机制和其他实验。这个 从分析核心和研究项目中得到的关于先导化合物的数据将由 MCLDC推动迭代导联优化和体内PK研究完成，产生优化导联 在动物研究中具有类似药物的特性。主要候选人将满足通过/不通过决策标准集 活性、效力和类似药物的特性。这一进程的最终结果的目标将是确定 适用于IND应用的新型优化的铅分子。MCLDC将纳入密钥 其他核心人员和研究项目团队的工作人员将被纳入优先次序和决策程序。

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.