权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Repurposing auranofin as antimicrobial to treat staphylococcal infections

将金诺芬重新用作抗菌剂来治疗葡萄球菌感染

基本信息

批准号：
9117837
负责人：
Mohamed Seleem
金额：
$ 37.63万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-15 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9117837
关键词：
Amebiasis Animal Model Anti-Bacterial Agents Anti-Inflammatory Agents Anti-inflammatory Antibiotic Resistance Antibiotics Auranofin Bacteria Bacterial Proteins Caring Centers for Disease Control and Prevention (U.S.)Cessation of life Chronic Clinical Clinical Trials Data Decubitus ulcer Development Diabetic Foot Ulcer Dose FDA approved Floxuridine Foundations Goals Grant Healed Health Human Infection Infectious Skin Diseases Inflammatory Response Knowledge Label Lead Maps Medical Methods Microbial Biofilms Mitochondrial Proteins Modality Modeling Multi-Drug Resistance Mus Oral Orphan Drugs Pharmaceutical Preparations Pharmacology and Toxicology Process Production Protein Biosynthesis Public Health Reporting Research Research Personnel Resistance Risk Staphylococcal Infections Staphylococcus aureus Testing Therapeutic Agents Time Toxin Treatment Efficacy Uncertainty United States Work antimicrobial antimicrobial drug bactericide comparative efficacy cost diabetic disorder prevention drug development drug discovery drug efficacy ebselen efficacy testing fight against healing innovation methicillin resistant Staphylococcus aureus multi-drug resistant pathogen mutant novel novel strategies pathogen pre-clinical pressure research study wound

项目摘要

DESCRIPTION (provided by applicant): Nearly 11,000 people died last year alone from a methicillin-resistant Staphylococcus aureus (MRSA)-related infection in the United States; this figure represents nearly half of all fatalities caused by antibiotic-resistant bacteria. It is well established that currently approved antimicrobials are losing the battle in the fight against multidrug-resistant pathogens. Without a doubt, novel antimicrobials and novel approaches to develop them are urgently needed; however, new antimicrobials are becoming increasingly difficult to develop. Repurposing FDA-approved drugs, with well-characterized toxicology and pharmacology, to find new applications outside the scope of the original medical indication is a novel way to reduce both the time and cost associated with antimicrobial innovation. Studies proposed in this application build upon discoveries of the potent bactericidal activity of the non- antimicrobial drugs auranofin, ebselen and FdUrd, in an applicable clinical range, against highly multidrug- resistant Gram-positive pathogens, including MRSA. Our preliminary studies strongly suggest that repurposing these drugs as an antimicrobial agent to treat MRSA infections will leapfrog the drug development process and save years of expensive research. The fact that auranofin recently has been granted orphan-drug status from the FDA for treatment of human amebiasis, further validates our approach. The goal of this application is to further develop, optimize, and validate auranofin, ebselen, and FdUrd as potential treatment for MRSA infections. In addition, we will evaluate the therapeutic efficacy of these drugs in a mouse wound-model that closely approximates the condition of diabetic foot ulcers in humans; this is expected to advance current knowledge in chronic wound care. Our findings in MRSA will be broadly relevant to other important pathogens impacting global public health. Furthermore, our work to repurpose these drugs should significantly impact and inform efforts by other researchers to repurpose other therapeutic agents as visible treatment options for multidrug-resistant pathogens.

描述（由申请人提供）：仅去年一年，美国就有近11，000人死于耐甲氧西林金黄色葡萄球菌（MRSA）相关感染;这一数字占耐甲氧西林细菌引起的所有死亡人数的近一半。公目前批准的抗菌药物正在失去与多重耐药病原体的斗争。毫无疑问，迫切需要新的抗菌剂和开发它们的新方法;然而，新的抗菌剂的开发变得越来越困难。重新利用FDA批准的药物，具有良好的毒理学和药理学特征，以在原始医学适应症范围之外寻找新的应用，是减少与抗菌药物创新相关的时间和成本的新方法。本申请中提出的研究建立在非细菌的有效杀菌活性的发现之上在一个实施方案中，本发明涉及抗微生物药物金诺芬（auranofin）、依布硒啉（ebselen）和FdUrd，其在适用的临床范围内针对高度多药耐药的革兰氏阳性病原体，包括MRSA。我们的初步研究强烈表明，将这些药物重新用作抗微生物剂来治疗MRSA感染将跨越药物开发过程，并节省多年的昂贵研究。事实上，金诺芬最近已被FDA授予治疗人类阿米巴病的新药地位，进一步验证了我们的方法。本申请的目的是进一步开发、优化和验证金诺芬、依布硒啉和FdUrd作为MRSA感染的潜在治疗药物。此外，我们将评估这些药物在小鼠伤口模型中的治疗效果，该模型非常接近人类糖尿病足溃疡的状况;预计这将推进慢性伤口护理的现有知识。我们在MRSA中的发现将与影响全球公共卫生的其他重要病原体广泛相关。此外，我们重新利用这些药物的工作应该会显著影响和通知其他研究人员重新利用其他治疗药物作为多药耐药病原体的可见治疗选择的努力。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates.

DOI：
10.1371/journal.pone.0164227
发表时间：
2016
期刊：
PloS one
影响因子：
3.7
作者：
AbdelKhalek A;Ashby CR Jr;Patel BA;Talele TT;Seleem MN
通讯作者：
Seleem MN

In Vitro Screening of an FDA-Approved Library Against ESKAPE Pathogens.

DOI：
10.2174/1381612823666170209154745
发表时间：
2017
期刊：
Current pharmaceutical design
影响因子：
3.1
作者：
Younis W;AbdelKhalek A;Mayhoub AS;Seleem MN
通讯作者：
Seleem MN

Drug repurposing for the treatment of staphylococcal infections.

DOI：
10.2174/1381612821666150310104416
发表时间：
2015
期刊：
Current pharmaceutical design
影响因子：
3.1
作者：
Thangamani S;Mohammad H;Younis W;Seleem MN
通讯作者：
Seleem MN

Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus.

DOI：
10.1038/srep29707
发表时间：
2016-07-11
期刊：
Scientific reports
影响因子：
4.6
作者：
Mohamed MF;Abdelkhalek A;Seleem MN
通讯作者：
Seleem MN

Antibacterial activity and mechanism of action of auranofin against multi-drug resistant bacterial pathogens.

DOI：
10.1038/srep22571
发表时间：
2016-03-03
期刊：
Scientific reports
影响因子：
4.6
作者：
Thangamani S;Mohammad H;Abushahba MF;Sobreira TJ;Hedrick VE;Paul LN;Seleem MN
通讯作者：
Seleem MN