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，但其作为起疱剂的作用机制仍然未知;此外，迄今为止，还没有有效的医疗对策来对抗战争起疱剂。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硫芥中毒的药物。在与当地一家制药公司和巴特尔纪念研究所的合作研究中，我们已经确定了两类可以预防或逆转硫芥毒性的候选药物。每类药物中至少有一种已被FDA批准用于其他适应症。在这种学术/工业合作伙伴关系中，计划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硫芥子气毒性模型系统的有效性。此外，还提出了研究和开发项目，旨在确定硫芥的具体作用机制和三个主要起泡剂靶点（眼睛、皮肤和肺）的潜在新靶点。这些项目的研究人员将与药理学和药物开发核心以及药物化学和药学核心密切合作，在药物开发方面具有相当的专业知识，为促进硫芥对策的发展提供见解。PI、co-Pi、PI研究和开发项目的研究实验室，药剂学 集团和药理学和药物开发中心位于罗格斯大学的布施校园内。他们都是环境和职业健康科学研究所（EOHSI）的成员，该研究所是由UMDNJ罗伯特·伍德约翰逊医学院和罗格斯大学药学院联合赞助的一个机构。EOHSI被指定为NIEHS卓越中心。药物化学组位于利哈伊大学，距离罗格斯大学约25英里。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。提出了一项培训和教育方案，将针对罗格斯大学药学院、UMDNJ公共卫生学院、UMDNJ罗伯特·伍德约翰逊医学院和利哈伊大学健康科学方案的卫生保健提供者。

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.