In vivo Core

项目摘要 大型制药公司的抗菌药物创新已经放缓，耐药感染激增，威胁公共卫生。威斯康星州抗菌剂的首要目标是 药物发现和开发中心是制定治疗对策，以解决抗菌药物 抵抗危机根据我们的初步数据，我们假设，共生的天然产品开发 环境使用互补的尖端方法将提供一个新的范例，发现新的 针对耐药感染的抗菌药物。该中心提出了创新的概念和技术 在克服传统抗微生物药物发现平台中发现的关键瓶颈方面取得了进展。的 这一奋进的成功取决于预测共生菌的抗菌效果的能力 天然产品在患者体内核心将评估体内微生物学有效性，哺乳动物 安全性，药代动力学和药效学的有前途的新的天然产物支架从每一个 中心项目（1、2、3）。核心使用临床相关的鼠感染模型， 靶向耐药病原体-革兰氏阴性细菌和真菌。这些核心活动的成果 将预测哪些化合物对耐药病原体具有有希望的体外活性， 临床上有用的抗微生物药物的进展。核心服务还将提供数据， 问题：在我们的三个CETR项目中，哪一种新的发现方法最好地提供了铅 抗菌化合物。阐明最佳的发现策略将产生一个变革性的和持续的 对新药开发的影响。

Project Summary Antimicrobial innovation by larger pharmaceutical companies has slowed while an epidemic of antimicrobialresistant infections surges, threatening the public health. The overarching goal of the Wisconsin Antimicrobial Drug Discovery and Development Center is to develop therapeutic countermeasures to tackle the antimicrobial resistance crisis. Based upon our preliminary data, we hypothesize that natural product exploration of symbiotic environments using complementary cutting-edge approaches will provide a new paradigm for discovery of novel antimicrobials targeting drug resistant infections. The Center proposes innovative conceptual and technical advances to overcome critical bottlenecks identified in traditional antimicrobial drug discovery platforms. The success of this endeavor is dependent upon the ability to predict antimicrobial effectiveness of the symbiotic natural products in patients. The In vivo Core will assess the in vivo microbiologic effectiveness, mammalian safety, pharmacokinetics and pharmacodynamics of promising novel natural product scaffolds from each Project (1, 2, 3) in the Center. The Core uses clinically relevant murine infection models with each of the target, drug-resistant pathogens – Gram negative bacteria and fungi. The results from these Core activities will predict which compounds with promising in vitro activity against drug-resistant pathogens are likely to progress to a clinically useful antimicrobial drug. The core services will also provide data that answer the question: which of the novel discovery approaches employed by our three CETR projects best delivers lead antimicrobial compounds. Elucidation of optimal discovery strategies will yield a transformative and sustained impact on the development of new drugs.