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; 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.

项目摘要 较大的制药公司的抗菌创新速度放慢了，而抗菌素抗性感染的流行也有威胁到公共卫生。威斯康星州抗菌素的总体目标 药物发现与开发中心是开发治疗对策，以应对抗菌素 抵抗危机。根据我们的初步数据，我们假设对符号的天然产品探索 使用完整的尖端方法的环境将为发现新颖的范式提供新的范式 靶向抗药性感染的抗菌素。该中心提议创新的概念和技术 克服传统抗菌药物发现平台中确定的关键瓶颈的进步。这 这项工作的成功取决于预测共生抗菌效率的能力 患者的天然产物。体内核心将评估体内微生物学的有效性，哺乳动物 诺言的安全，药代动力学和药效学的新型天然产品支架 中心的项目（1、2、3）。核心使用临床相关的鼠感染模型 靶标，耐药病原体 - 革兰氏阴性细菌和真菌。这些核心活动的结果 将预测哪些具有对药物抗药性病原体的体外活性有望的化合物可能会 发展为临床上有用的抗菌药物。核心服务还将提供回答的数据 问题：我们的三个Cetr项目最佳销售铅的新颖发现方法中的哪种方法 抗菌化合物。阐明最佳发现策略将产生变革性和持续性 对新药开发的影响。