In vivo Core

体内核心

• 批准号: 10592383
• 负责人: David R Andes
• 金额: $ 63.48万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592383
• 关键词: vivo; Core

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.

项目概要 大型制药公司的抗菌药物创新已经放缓，而抗菌药物耐药性感染的流行却激增，威胁着公众健康威斯康星州抗菌药物的总体目标。 药物发现和开发中心将制定治疗对策以应对抗菌药物 根据我们的初步数据，我们进行了共生天然产品的探索。 使用互补的尖端方法的环境将为发现新颖的事物提供新的范式 该中心提出了针对耐药感染的创新概念和技术。 克服传统抗菌药物发现平台中发现的关键瓶颈的进展。 这项努力的成功取决于预测共生菌抗菌效果的能力 体内核心将评估哺乳动物体内的天然产品。 每个有前途的新型天然产物支架的安全性、药代动力学和药效学 该中心的项目 (1, 2, 3) 使用临床相关的小鼠感染模型。 目标耐药病原体 – 革兰氏阴性细菌和真菌 这些核心活动的结果。 将预测哪些化合物可能具有针对耐药病原体的体外活性 临床上有用的抗菌药物的进展也将提供回答这些问题的数据。 问题：我们的三个 CETR 项目采用的哪种新颖的发现方法最能发挥领先作用 阐明最佳发现策略将产生变革性和持续性的结果。 对新药研发的影响。