Discovery and validation of broadly effective LpxH inhibitors as novel therapeutics against multi-drug resistant Gram-negative pathogens
广泛有效的 LpxH 抑制剂的发现和验证作为针对多重耐药革兰氏阴性病原体的新疗法
基本信息
- 批准号:10322657
- 负责人:
- 金额:$ 45.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-02-01 至 2023-01-31
- 项目状态:已结题
- 来源:
- 关键词:Acinetobacter baumanniiAminoglycosidesAnabolismAntibiotic TherapyAntibioticsBacteremiaBacteriaBiological AssayCampylobacterCarbapenemsCephalosporinsChemicalsClinicalComplexDermatitisDevelopmentDiffusionDrug TargetingDrug resistanceEnterobacteriaceaeEnzyme InhibitionEnzyme Inhibitor DrugsEnzymesEscherichia coliExtended-spectrum β-lactamaseFluoroquinolonesGenesGoalsGram-Negative BacteriaHaemophilus influenzaeHealthHelicobacter pyloriHospitalsHumanHydrolaseImmunocompromised HostIn VitroInfectionKlebsiella pneumoniaeLeadLipid ALipidsMeasurementMeasuresMembraneMulti-Drug ResistanceNeisseria gonorrhoeaeOrganismOsteomyelitisPathway interactionsPatientsPharmaceutical PreparationsPseudomonas aeruginosaPublic HealthRefractoryReportingResistanceRespiratory SystemSafetyShigellaSoft Tissue InfectionsStructureSurfaceSystemic infectionTetracyclinesToxic effectUrinary tract infectionValidationVancomycin resistant enterococcusX-Ray Crystallographyantimicrobialantimicrobial drugassay developmentbiophysical propertiescarbapenem resistancecheminformaticsclinical developmentcytotoxicityefflux pumpgastrointestinal infectionhigh throughput screeningin vivoinhibitorjoint infectionlead optimizationlipid biosynthesismethicillin resistant Staphylococcus aureusmulti-drug resistant pathogennovelnovel therapeuticsopportunistic pathogenpathogenpublic health relevanceresistance mechanismscreeningsmall molecule inhibitor
项目摘要
Project Summary/Abstract
An alarming number of Gram-negative nosocomial pathogens have acquired resistance to nearly all currently
available antibiotics, making it very difficult to treat patients effectively. Moreover, in the last decade, only a
handful of new antimicrobial agents have been introduced, and these have mostly targeted drug-resistant
Gram-positive pathogens such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci
(VRE). The goal of this proposal is to develop a high-throughput screening assay to discover and validate small
molecule inhibitors of LpxH, an essential enzyme in the lipid A biosynthetic pathway, as novel antibiotics for the
treatment of infections caused by multidrug-resistant Gram-negative pathogens.
项目摘要/摘要
目前,数量惊人的革兰氏阴性医院内病原菌已对几乎所有
可获得的抗生素,使有效治疗患者变得非常困难。此外,在过去的十年中,只有一个
已经推出了几种新的抗菌剂,这些抗菌剂大多针对抗药性
革兰氏阳性病原菌,如耐甲氧西林金黄色葡萄球菌(MRSA)和耐万古霉素肠球菌
(Vre)。这项提案的目标是开发一种高通量筛查试验,以发现和验证小分子
LpxH的分子抑制剂,LpxH是脂质A生物合成途径中的一种关键酶,作为治疗癌症的新型抗生素
多重耐药革兰氏阴性菌感染的治疗。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Structure-Activity Relationship of Sulfonyl Piperazine LpxH Inhibitors Analyzed by an LpxE-Coupled Malachite Green Assay.
- DOI:10.1021/acsinfecdis.8b00364
- 发表时间:2019-02
- 期刊:
- 影响因子:5.3
- 作者:Minhee Lee;Jinshi Zhao;Seung‐Hwa Kwak;J. Cho;M. Lee;R. Gillespie;D. Kwon;Hyunji Lee;Hyun-Ju Park;Qinglin Wu;P. Zhou;Jiyong Hong
- 通讯作者:Minhee Lee;Jinshi Zhao;Seung‐Hwa Kwak;J. Cho;M. Lee;R. Gillespie;D. Kwon;Hyunji Lee;Hyun-Ju Park;Qinglin Wu;P. Zhou;Jiyong Hong
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Pei Zhou其他文献
Pei Zhou的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Pei Zhou', 18)}}的其他基金
Mechanistic Insights into the Plant Disease Resistance Mediated by NPR1
NPR1 介导的植物抗病性的机制见解
- 批准号:
10793966 - 财政年份:2022
- 资助金额:
$ 45.83万 - 项目类别:
Mechanistic Insights into the Plant Disease Resistance Mediated by NPR1
NPR1 介导的植物抗病性的机制见解
- 批准号:
10390811 - 财政年份:2022
- 资助金额:
$ 45.83万 - 项目类别:
Mechanistic Insights into the Plant Disease Resistance Mediated by NPR1
NPR1 介导的植物抗病性的机制见解
- 批准号:
10670797 - 财政年份:2022
- 资助金额:
$ 45.83万 - 项目类别:
Structural and Biochemical Studies of LpxC Inhibition
LpxC 抑制的结构和生化研究
- 批准号:
7846499 - 财政年份:2009
- 资助金额:
$ 45.83万 - 项目类别:
Structural, Biochemical and Functional Studies of RNAPII CTD Interacting Proteins
RNAPII CTD 相互作用蛋白的结构、生化和功能研究
- 批准号:
7904244 - 财政年份:2008
- 资助金额:
$ 45.83万 - 项目类别:
Structural, Biochemical and Functional Studies of RNAPII CTD Interacting Proteins
RNAPII CTD 相互作用蛋白的结构、生化和功能研究
- 批准号:
7526527 - 财政年份:2008
- 资助金额:
$ 45.83万 - 项目类别:
Structural, Biochemical and Functional Studies of RNAPII CTD Interacting Proteins
RNAPII CTD 相互作用蛋白的结构、生化和功能研究
- 批准号:
7679450 - 财政年份:2008
- 资助金额:
$ 45.83万 - 项目类别:
Structural, Biochemical and Functional Studies of RNAPII CTD Interacting Proteins
RNAPII CTD 相互作用蛋白的结构、生化和功能研究
- 批准号:
8118895 - 财政年份:2008
- 资助金额:
$ 45.83万 - 项目类别:
Structural and Biochemical Studies of LpxC Inhibition
LpxC 抑制的结构和生化研究
- 批准号:
8239580 - 财政年份:2003
- 资助金额:
$ 45.83万 - 项目类别:
相似海外基金
Aminoglycosides with reduced ototoxicity via miRNA targeting
通过 miRNA 靶向降低耳毒性的氨基糖苷类药物
- 批准号:
9891947 - 财政年份:2019
- 资助金额:
$ 45.83万 - 项目类别:
Aminoglycosides with reduced ototoxicity via miRNA targeting
通过 miRNA 靶向降低耳毒性的氨基糖苷类药物
- 批准号:
9982540 - 财政年份:2019
- 资助金额:
$ 45.83万 - 项目类别:
Antibacterial properties of amphiphilic aminoglycosides
两亲性氨基糖苷类药物的抗菌特性
- 批准号:
524825-2018 - 财政年份:2018
- 资助金额:
$ 45.83万 - 项目类别:
University Undergraduate Student Research Awards
Nanobiocapteurs de résonance des plasmons de surface pour les aminoglycosides
氨基糖苷类表面等离激元共振的纳米生物捕获剂
- 批准号:
495915-2016 - 财政年份:2016
- 资助金额:
$ 45.83万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Master's
Designing new aminoglycosides to alleviate inner ear toxicity
设计新的氨基糖苷类药物以减轻内耳毒性
- 批准号:
8943277 - 财政年份:2015
- 资助金额:
$ 45.83万 - 项目类别: