UMDNJ/Rutgers University CounterACT Research Center of Excellence

硫芥是一种强效的化学战泡腾剂，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，但其作为一种发泡剂的作用机制仍然未知；此外，到目前为止，还没有有效的医疗对策来对付接触战争发泡剂。拟议中的UMDNJ/Rutgers大学反作用研究卓越中心将专门专注于开发治疗芥子气中毒的药物。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，我们已经确定了两种候选药物，可以预防或逆转硫芥毒性。每一类药物中至少有一种已经被FDA批准用于其他适应症。在这个学术/工业合作伙伴关系中，计划从我们已经确定的基团中优化先导化合物，确定活性药效团，并最终合成结构异构体。我们还将在芥菜毒性模型系统中评估这些潜在对策的有效性。此外，还提出了研究和开发项目，旨在确定硫磺芥的具体作用机制和潜在的新靶点，以治疗干预三个主要的目标：眼睛、皮肤和肺。这些项目的研究人员将与具有药物开发专业知识的药理学和药物开发核心以及药物化学和药物学核心密切合作，为促进芥子气对策的开发提供见解。PI的研究实验室，PI的合作实验室，PI的研究和发展项目实验室，药剂学实验室

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.