UMDNJ/Rutgers University CounterACT Research Center of Excellence

芥子气是一种强有力的化学战发泡剂，被认为是一种高度优先的化学威胁。 虽然它已经被研究了80多年，但其作为发泡剂的作用机制 仍然未知;此外，迄今为止，没有针对战争暴露的有效医疗对策 水疱剂。拟议中的UMDNJ/罗格斯大学反ACT卓越研究中心将 专门致力于开发治疗芥子气中毒的药物。在合作研究中， 一家当地的制药公司和巴特尔纪念研究所，我们已经确定了两个候选类， 可以预防或逆转硫芥毒性的药物。每个类别中至少有一个成员 该药物此前已被FDA批准用于其他适应症。在这个学术/工业 合作伙伴关系，计划是从我们已经确定的组中优化先导化合物，以确定 活性药效团，并最终合成结构异构体。我们还将评估 这些潜在的对策在模型系统的硫芥子气毒性。此外，研究和 提出了旨在确定硫的具体作用机制的开发项目 芥子气和潜在的新的治疗干预目标，在三个主要的起泡剂目标：眼睛， 皮肤和肺。这些项目的研究人员将与药理学和药物管理局密切合作。 开发核心和药物化学和制药核心，具有相当的药物专业知识 发展，提供见解，以促进硫芥子气对策的发展。的 PI的研究实验室，合作PI，研究和开发项目的PI，药剂学 集团和药理学和药物开发核心位于彼此非常接近的 罗格斯大学布希校区。他们都是环境和职业健康委员会的成员。 科学研究所（EOHSI），由UMDNJ-罗伯特伍德约翰逊医学院联合赞助的设施 和罗格斯大学药学院。EOHSI已被指定为NIEHS中心， 卓越药物化学组位于利哈伊大学，距离 罗格斯大学。私家侦探这个中心（J.拉斯金）和PI。药物化学核心（N。 Heindel）由NIEHS共同资助药物开发赠款超过15年。一个培训和 教育计划提出，将针对医疗保健提供者在罗格斯大学医学院 药学，UMDNJ-公共卫生学院，UMDNJ-罗伯特伍德约翰逊医学院和健康 理哈伊大学的科学课程。

Sulfur mustard, a potent chemical warfare vesicant, is considered to be a high priority chemical threat. Although it has been studied for more than 80 years, the mechanisms mediating its actions as a vesicant remain unknown; moreover, to date, there are no effective medical countermeasures for exposure to warfare vesicants. The proposed UMDNJ/Rutgers University CounterACT Research Center of Excellence will specifically focus on the development of drugs to treat sulfur mustard poisoning. In collaborative studies with a local pharmaceutical company and Battelle Memorial Institute, we have identified two candidate classes of Pharmaceuticals that can prevent or reverse sulfur mustard toxicity. At least one member of each class of drugs has previously been approved by the FDA for other indications. In this academic/industrial partnership, plans are to optimize the lead compounds from the groups we have identified, to determine the active pharmacophores, and ultimately to synthesize structural isomers. We will also evaluate the efficacy of these potential countermeasures in model systems of sulfur mustard toxicity. In addition, Research and Development Projects are proposed that are designed to identify specific mechanisms of action of sulfur mustard and potential new targets for therapeutic intervention in three major vesicant targets: the eye, the skin and the lung. Investigators on these projects will work closely with a Pharmacology and Drug Development Core and a Medicinal Chemistry and Pharmaceutics Core with considerable expertise in drug development, providing insights to facilitate the development of sulfur mustard countermeasures. The research laboratories of the PI, co-Pi, Pi's of the Research and Development Projects, the Pharmaceutics group and Pharmacology and Drug Development Core are located in close proximity to one another on the Busch campus of Rutgers University. They are all members of the Environmental and Occupational Health Sciences Institute (EOHSI), a facility jointly sponsored by UMDNJ-Robert Wood Johnson Medical School and the School of Pharmacy at Rutgers University. EOHSI has been designated as an NIEHS Center of Excellence. The Medicinal Chemistry group is located at Lehigh University, approximately 25 miles from Rutgers University. The P.I. of this Center (J. Laskin) and the P.I. of the Medicinal Chemistry Core (N. Heindel) have been jointly funded by NIEHS on drug development grants for over 15 years. A Training and Education Program is proposed that will be directed at health care providers at Rutgers University School of Pharmacy, UMDNJ-School of Public Health, UMDNJ-Robert Wood Johnson Medical School and the Health Sciences Program at Lehigh University.