Scientific Core - Pharmacology and Drug Development

科学支持核心：药理学和药物开发 主要人员： Diane E.Heck，博士，核心主管： Lauren M.Aleksunes，药学博士，临床前科学小组主任 朱尔斯·米切尔，博士，翻译小组主任 罗伯特·卡西利亚斯，博士，临床前疗效焦点小组联合负责人 迈克尔·A·加洛，博士，临床前疗效焦点小组联合负责人 帕特里克·辛科，R.Ph，博士，ADME和毒理学焦点小组联合负责人 Glen Park，药学博士，监管事务焦点团队联席主管 Neal Simon，博士，翻译到高级开发焦点团队负责人 核心摘要/摘要 罗格斯中和中心药理学和药物开发促进发展的核心 治疗皮肤、角膜和肺损伤的治疗方法 化学威胁物质硫磺芥末和氮芥末。这一核心一直与中心密切合作 调查人员对候选药物进行识别、表征和优先排序，评估毒理学特征，并 先导候选药物的药代动力学特性，并确定最佳给药途径，与 目的是生成数据以支持研究新药(IND)申请和临床试验。核心是 被组织成四个重点小组，每个小组服务于对药物开发至关重要的特定职能：临床前 药效、ADME和毒理学、管理事务和高级药物开发的翻译。这个 目前由Core协调的流水线包括炎症靶标的调节剂，包括基质 金属蛋白酶(强力环素)肿瘤坏死因子α(抗肿瘤坏死因子α抗体，己酮可可碱)，诱导型一氧化氮合酶 (氨基胍)和COX-2/胆碱酯酶(NDH4338)，将减少损伤和/或促进伤口愈合 暴露于芥末后的肺、角膜或皮肤。药物产品正在迅速发展，有几个 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IND前与FDA办公室就反恐和紧急情况举行会议的产品 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 及时、高效地推进产品进度。在这份续期申请中，我们建议提前 第一代药物(肿瘤坏死因子α拮抗剂、多西环素和一种非甾体抗炎药前药)的数量 监管部门的批准。管道中的其他化学物质继续作为第二代进行研究 药效提高的药品。预计未来5年将提高核心的利用率，因为 作为对芥末毒性的对策，该中心正在将一些产品转入高级开发阶段。

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.