Rutgers University CounterACT Center of Excellence

摘要 这是罗格斯大学对抗卓越研究中心的续签申请， 在发现和开发治疗暴露于化学威胁剂的中毒的药物方面处于领先地位。 该中心专注于发泡剂，包括硫磺芥末、氮芥末和其他与机械相关的 并被组织为三个研究和开发项目，每个项目侧重于一种主要的发泡剂 目标：皮肤、角膜和肺。该中心的总体目标是确定这些目标中的具体目标 可用于治疗干预的组织。为了实现这一目标，机械学研究使用 科学专家正在对皮肤、角膜和肺进行适当的翻译模型 这些地区。研究和开发项目由一个药理学和药物研究所提供支持 发展科学支持核心和制药和药物化学科学支持核心， 每个机构都由在药物发现、输送和开发方面具有相当专业知识的调查人员组成。 通过机理研究，罗格斯中心发现并优先考虑了几种有效的引线 化合物和2)开发了创新的制剂和递送系统，以增强药理作用 活性和改善药代动力学曲线。三种先导化合物，两种用于芥末引起的眼睛损伤 另一种用于芥末引起的肺损伤，FDA已批准用于其他适应症，并正在推进中 用作芥末对策。此外，还在一个领先位置上完成了支持IND的研究 一种化合物被发现对芥末引起的皮肤损伤有效。罗格斯大学反制中心 与先导化合物建立了先进药物开发的战略企业合作伙伴关系 由BARDA提供支持。面向学生、博士后实习生、技术人员和 新的和成熟的调查人员在培训熟练的劳动力方面取得了极大的成功 对策。在下一次资助期间，我们将1)鉴定和开发第二代药物 有效性提高的产品，2)传播关于毒性机制的关键发现和新的 测试策略和模型，3)通过FDA审批程序推进当前药物的领先地位，4)扩展 培训和劳动力发展机会。通过满足关键的研究、开发和培训 作为里程碑，该中心已做好准备，通过批准程序推进新药和重新调整用途的药物 治疗人体发泡剂中毒。

Abstract This is a renewal application for the Rutgers University CounterACT Research Center of Excellence, leaders in the discovery and development of drugs to treat poisoning from exposure to chemical threat agents. The Center focuses on vesicants including sulfur mustard, nitrogen mustard, and other mechanistically related chemicals and is organized into three Research and Development Projects, each focused on a major vesicant target: the skin, the cornea and the lung. The overall goal of the Center is to identify specific targets in these tissues that can be used for therapeutic intervention. To accomplish this goal, mechanistic research using appropriate translational models for the skin, cornea and lung is being performed by scientific experts in each of these areas. The Research and Development Projects are supported by a Pharmacology and Drug Development Scientific Support Core and a Pharmaceutics and Medicinal Chemistry Scientific Support Core, each consisting of investigators with considerable expertise in drug discovery, delivery and development. Through mechanistic research, the Rutgers Center has 1) discovered and prioritized several efficacious lead compounds and 2) developed innovative formulations and delivery systems that augment pharmacological activity and improve pharmacokinetic profiles. Three lead compounds, two for mustard-induced ocular injury and another for mustard-induced lung injury, are FDA approved for other indications, and are being advanced for use as mustard countermeasures. Furthermore, IND-enabling studies have been completed on a lead compound discovered to be effective against mustard-induced skin injury. The Rutgers CounterACT Center has established strategic corporate partnerships for advanced drug development with lead compounds and support by BARDA. A Research Education Core directed at students, postdoctoral trainees, technical staff, and new and established investigators has been highly successful at training a skilled workforce in countermeasures. During the next grant period, we will 1) identify and develop second generation drug products with improved effectiveness, 2) disseminate key findings about mechanisms of toxicity and novel testing strategies and models, 3) advance current drug leads through the FDA approval process and 4) expand training and workforce development opportunities. By meeting key research, development, and training milestones, the Center is well-poised to advance new and repurposed drugs through the approval process for treating vesicant poisoning in humans.