Antimicrobial Oligomers for BioDefense and Emerging Food Borne Infectious Disease

用于生物防御和新兴食源性传染病的抗菌低聚物

• 批准号: 7645326
• 负责人: Gregory N. Tew
• 金额: $ 97.77万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7645326
• 关键词: Acute; Address; Anti-Bacterial Agents; Antibiotics; Bacteria; Categories; Communicable Diseases; Drug Formulations; Drug Kinetics; Evaluation; Goals; Immune system; Immunity; Instruction; Lead; Listeria monocytogenes; Membrane; Metabolic; Molecular; National Institute of Allergy and Infectious Disease; Organism; Pharmacology and Toxicology; Play; Property; Resistance development; Role; Salmonella; Schedule; Shigella; Sodium Chloride; Toxic effect; Translating; Vibrio; Yersinia enterocolitica; antimicrobial; antimicrobial peptide; base; biodefense; design; drug development; experience; foodborne; foodborne pathogen; in vivo; natural antimicrobial; novel; novel strategies; pre-clinical; programs; scaffold; scale up

DESCRIPTION (provided by applicant): To address the pressing need for broad spectrum, novel antibiotics, we will build on important preliminary results to design and optimize AMOs against food-borne pathogens, importantly expanding the scope of previous results to treat Gram-negative organisms. To this end, we have identified three molecular scaffolds with good preliminary activity and these will be further developed The fundamental mechanism for antibacterial activity including the role of the membranes and membrane components, the ability or inability of bacteria to develop resistance to these new AMOs and the role these AMOs play on the innate and/or adaptive immune system will be determined. The goal is to identify compounds, or compound classes, that demonstrate potent antibacterial in vivo efficacy against Category B food-borne pathogens without obvious toxicity. Acute toxicity, pharmacokinetic properties, metabolic stability and in vivo efficacy of the lead compounds will be evaluated. The results from these studies will be used to select a lead compound for complete drug development evaluations suitable for regulatory submission. The ultimate goal of the program is to complete all studies necessary to enable IND filing. Based on our previous experience in which we translated an AMO from initial discovery to an approved Canadian CTA in 5 years, the proposed schedule is reasonable and appropriate. RELEVANCE (See instructions): The need for new antibiotics is pressing and developing broad spectrum agents is a key initiative of NIAID. Our novel approach to identifying leads which capture the antimicrobial activity of natural antimicrobial peptides has already inability on CTA approval. Here the focus is on Gram-negative organisms.

描述（由申请人提供）：为了满足对广泛的抗生素的紧迫需求，我们将以重要的初步结果为基础，以设计和优化AMO，以针对粮食传播的病原体进行优化，重要的是扩大了先前结果的范围，以治疗革兰氏阴性生物体。为此，我们已经确定了三个具有良好初步活动的分子支架，这些分子支架将进一步开发出抗菌活性的基本机制，包括膜和膜成分的作用，细菌的能力或无力发展对这些新AMOS的抵抗以及这些AMOS在天生和///适应系统上的作用将确定这些AMOS的作用。目的是识别表现出对B类食物传播病原体的体内疗效有效的化合物或化合物类别，而没有明显的毒性。将评估急性毒性，药代动力学特性，代谢稳定性和铅化合物的体内功效。这些研究的结果将用于选择适合调节性提交的完整药物开发评估的铅化合物。该计划的最终目标是完成启用IND申请所需的所有研究。根据我们以前的经验，在5年内，我们将AMO从初始发现转换为批准的加拿大CTA，提议的时间表是合理且适当的。相关性（请参阅说明）：新抗生素的需求是紧迫和发展广谱剂是NIAID的关键倡议。我们的新方法识别铅捕获天然抗菌肽的抗菌活性的铅方法已经无法获得CTA批准。这里的重点是革兰氏阴性生物。