Scientific Core - Pharmacology and Drug Development

科学支持核心：药理学和药物开发 关键人员： 黛安·E Heck博士，核心总监： 劳伦M. Aleksunes，药学博士，哲学博士、临床前科学组总监 朱尔斯·米切尔博士，翻译组主任 罗伯特·卡西利亚斯博士，临床前疗效重点团队共同负责人 Michael A.加洛博士，临床前疗效重点团队共同负责人 帕特里克辛科，R. Ph.，哲学博士、ADME和毒理学焦点团队共同负责人 Glen Park，药学博士，法规事务重点团队联合负责人 尼尔·西蒙博士负责人，高级开发焦点团队翻译 核心摘要/摘要 罗格斯大学反ACT中心药理学和药物开发核心，促进发展 用于治疗暴露于两种高度优先的 化学威胁剂，硫芥子气和氮芥子气。这个核心一直与中心密切合作， 研究人员识别、表征和优先考虑候选药物，评估毒理学特征， 的药物动力学特性，并确定最佳的药物输送方法，与 目的是生成数据，以支持研究性新药（IND）申请和临床试验。核心是 组织成四个重点团队，每个团队都有一个对药物开发至关重要的特定职能： 疗效、ADME和毒理学、法规事务和高级药物开发翻译。的 目前由核心协调的管道包括炎症靶点的调节剂，包括基质金属蛋白酶， 金属蛋白酶类（多西环素）TNFα（抗TNF α抗体，戊茶碱），诱导型一氧化氮合酶 （氨基胍）和考克斯-2/胆碱酯酶（NDH 4338），其将减少损伤和/或促进 肺、角膜或皮肤暴露于吗啡后。药物产品正在迅速发展， 接近准备过渡到高级开发，包括临床研究。其中包括药物 导致与FDA反恐和紧急情况办公室举行IND前会议的产品 协调人员（CTECS）和FDA的药物评价和研究中心（CDER）。核心 与合同研究组织和制药公司以及监管机构合作，以确保 产品的及时和高效的发展。在这次更新申请中，我们建议提前一个 许多第一代药物产品（TNFα拮抗剂、多西环素和NSAID前药） 监管批准。管道中的其他化学实体继续作为第二代进行研究 提高疗效的药品。预计在今后五年内， 该中心正在将一些产品作为芥末毒性的对策进行高级开发。

Scientific Support Core: Pharmacology and Drug Development Key Personnel: Diane E. Heck, Ph.D., Core Director: Lauren M. Aleksunes, Pharm.D., Ph.D., Director, Preclinical Science Group Jules Mitchel, Ph.D., Director, Translational Group Robert Casillas, Ph.D., Co-Leader, Preclinical Efficacy Focus Team Michael A. Gallo, Ph.D., Co-leader, Preclinical Efficacy Focus Team Patrick Sinko, R.Ph., Ph.D., Co-leader, ADME and Toxicology Focus Team Glen Park, Pharm.D., Co-Leader, Regulatory Affairs Focus Team Neal Simon, Ph.D., Leader, Translation to Advanced Development Focus Team Core Summary/Abstract The Rutgers CounterACT Center Pharmacology and Drug Development Core that facilitates the development of therapeutics for treatment of skin, cornea and lung injury resulting from exposure to two high priority chemical threat agents, sulfur mustard and nitrogen mustard. This Core have been working closely with Center investigators to identify, characterize and prioritize drug candidates, evaluate the toxicological profile and pharmacokinetic properties of lead drug candidates, and determine optimal drug delivery approaches, with the aim of generating data to support Investigational New Drug (IND) applications and clinical trials. The Core is organized into four focus teams, each serving a specific function critical to drug development: Preclinical Efficacy, ADME and Toxicology, Regulatory Affairs, and Translation to Advanced Drug Development. The current pipeline coordinated by the Core includes modulators of inflammatory targets including matrix metalloproteinases (doxycycline) TNFα (anti-TNFα antibody, pentoxifylline), inducible nitric oxide synthase (aminoguanidine), and COX-2/cholinesterase (NDH4338) that will reduce injury and/or promote healing of the lung, cornea, or skin following exposure to mustards. Drug products are rapidly progressing with several approaching readiness to transition to advanced development including clinical studies. These include drug products that have led to pre-IND meetings with the FDA office on Counter-Terrorism and Emergency Coordination Staff (CTECS) and the FDA's Center for Drug Evaluation and Research (CDER). The Core partners with contract research organizations and pharmaceutical companies, as well as regulators to ensure the timely and efficient progression of products. In this renewal application, we propose the advancement of a number of first generation drug products (TNFα antagonists, doxycycline, and an NSAID prodrug) towards regulatory approval. Additional chemical entities in the pipeline continue to be studied as second generation drug products with improved efficacy. Greater utilization of the Core is anticipated in the next 5 years as the Center is moving a number of products into advanced development as countermeasures for mustard toxicities.