Rutgers University CounterACT Center of Excellence

摘要 这是罗格斯大学反ACT卓越研究中心的更新申请， 在发现和开发药物治疗暴露于化学威胁剂中毒方面的领导者。 该中心的重点是vesicants，包括硫芥，氮芥，和其他机械相关 化学品，并组织成三个研究和发展项目，每一个重点放在一个主要的发泡剂 目标：皮肤、角膜和肺。该中心的总体目标是确定这些领域的具体目标， 可以用于治疗干预的组织。为了实现这一目标，机械研究使用 皮肤、角膜和肺的适当平移模型正在由每个国家的科学专家进行， 这些地区。研究和开发项目得到药理学和药物管理局的支持。 开发科学支持核心和制药学和药物化学科学支持核心， 每一个都由在药物发现、交付和开发方面具有相当专业知识的研究人员组成。 通过机理研究，罗格斯中心发现并优先考虑了几种有效的先导药物 化合物和2）开发了创新的配方和输送系统， 活性和改善药代动力学特征。三种先导化合物，两种用于芥子气引起的眼损伤 另一种用于芥子气引起的肺损伤，FDA已批准用于其他适应症， 用作芥子气对抗措施。此外，还完成了关于一个牵头项目的国家自主研发赋能研究， 该化合物被发现对芥末引起的皮肤损伤有效。Rutgers CounterACT中心 已经建立了战略性的企业合作伙伴关系，以开发具有先导化合物的先进药物， 由巴尔达支持。研究教育核心针对学生，博士后培训生，技术人员， 新的和现有的调查人员在培训熟练的工作人员方面非常成功， 对策在下一个资助期内，我们将1）确定和开发第二代药物 2）传播关于毒性机制的关键发现， 测试策略和模型，3）通过FDA批准程序推进当前药物领先地位，4）扩大 培训和劳动力发展机会。通过满足关键的研究、开发和培训 里程碑，该中心已做好准备，通过批准程序推进新的和重新用途的药物， 治疗人类的糜烂性中毒

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.