Core D: Medicinal Chemistry Core

摘要 MedChem核心D将主要关注非核苷直接作用抗病毒药物（DAA）的递送 以补充READDI-AC产品组合中现有的化学资产。 为了实现这一目标，MedChem Core D将创建高质量的非核苷小分子探针， 强大的抗病毒活性和药物样药代动力学特性。MedChem核心D由以下组成 美国和英国结构基因组联盟的实验和计算化学家 (SGC)他们在与科学界自由开发和分享方面有着一流的记录 化学探针和小分子药物线索。MedChem Core D生成的所有化学探针将 向AViDD中心和更广泛的研究社区提供，不受知识产权限制， 对每种DAA机制的治疗潜力和效用广度进行深入的科学研究。 MedChem Core D特别适合利用开放式医疗的创新和生产力提高， 支持其具体目标的科学： 目标1。命中发现支持：MedChem Core D将支持高通量筛选的命中分类 由Discovery Core B执行，并通过组装目标类化学品进行种子命中发现工作 基于结构的虚拟筛选（VS）和从头设计方法的文库。 目标二。命中探针：MedChem Core D将迭代设计具有理化性质的药物样类似物集 与细胞活动一致的特性。类似物将在一系列试验中进行评估，以解决 靶向亲和力、细胞活性、ADME性质和在病毒复制测定中的功效。最终探测器将 进行广泛表征，以支持其MoA和疗效，并进行体内PK分析， 铅CV。SGC开放化学网络将用于为这些目标提供额外的能力 两部以上的热门剧集 MedChem Core D的总体目标是提供至少16种具有强大抗肿瘤活性的化学探针。 病毒活性和类药物性质。这些探测器将作为引导候选人的起点 项目的优化。

ABSTRACT MedChem Core D will focus primarily on the delivery of non-nucleoside direct acting antiviral (DAA) leads to the Projects to complement the existing chemical assets in the READDI-AC portfolio. To achieve this goal MedChem Core D will create high-quality non-nucleoside small molecule probes with robust antiviral activity and drug-like pharmacokinetic properties. MedChem Core D is composed of experimental and computational chemists at the US and UK sites of the Structural Genomic Consortium (SGC) who have a track record in developing and sharing freely with the scientific community first-in-class chemical probes and small molecule drug leads. All chemical probes generated by MedChem Core D will be made available to the AViDD centers and the broader research community, unrestricted by IP, to enable deep scientific study of both therapeutic potential as well as breadth of utility of each DAA mechanism. MedChem Core D is particularly well placed to harness the innovation and productivity gains of open science to support its specific aims: Aim 1. Hit Discovery Support: MedChem Core D will support the hit triage of high throughput screens performed by Discovery Core B and seed hit discovery efforts through assembly of target class chemical libraries from structure-based virtual screening (VS) and de novo design approaches. Aim 2. Hit to probe: MedChem Core D will iteratively design sets of drug-like analogs with physiochemical properties consistent with cellular activity. Analogs will be assessed in a hierarchy of assays to address target affinity, cellular activity, ADME properties, and efficacy in virus replication assays. Final probes will be extensively characterized to support their MoA and efficacy and be profiled for in vivo PK to complete a Lead CV. The SGC Open Chemistry Network will be used to provide additional capacity for those targets that yield more than two confirmed hit series. The overall goal of the MedChem Core D is to deliver a minimum of 16 chemical probes with robust anti- viral activity and drug-like properties. These probes will serve as starting points for lead-to-candidate optimization by the Projects.