A Rapid assay for RNA targeted drugs: Instrumentation Supplement
RNA 靶向药物的快速检测:仪器补充
基本信息
- 批准号:9120576
- 负责人:
- 金额:$ 8.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-01 至 2018-03-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAffinityAmikacinAmino SugarsAminoglycosidesAnti-Bacterial AgentsAntibiotic ResistanceAntibiotic TherapyAntibioticsAntineoplastic AgentsAntiviral AgentsBacteriaBacterial InfectionsBindingBiological AssayCellsCessation of lifeClinicalCollaborationsDerivation procedureDermalDevelopmentDiseaseDrug TargetingEnvironmentEquilibriumEscherichia coliFibroblastsFluoresceinFluorescenceGrowthHIVHealthHospitalsHousingHumanImmune responseIndustryInfectionKanamycinLengthLibrariesLifeLiquid substanceMalignant NeoplasmsMedicalModelingNeomycinNucleic AcidsPathologyPharmaceutical PreparationsPhasePreparationRNAReaderReporterResearchRibosomesRobotSalesSiteSkinSouth CarolinaStructureSystemTechnologyTobramycinToxic effectUnited StatesUnited States National Institutes of HealthUniversitiesWorkantimicrobialbacterial resistancebaseclinically relevantcommercializationcostcytotoxicitydeprotonationdrug discoveryeffective therapyfunctional grouphigh throughput screeningin vivoinstrumentationkeratinocytenephrotoxicitynext generationnovelototoxicitypathogenresistant strainscreening
项目摘要
DESCRIPTION (provided by applicant): Some of the most significant therapies that treat disease target nucleic acids. Drugs that target nucleic acid include cancer drugs, antibiotics, and
antivirals. Combined these classes of drugs have annual sales worldwide of ~$139 billion. Antibiotics that target nucleic acids account for $14.5 billion of the $42 billion of sales annuall for all antibiotics, and account for three of the top five classes of antibiotics. The crisis of antibiotic resistance has resulted in a significant cost, both financially and in human life. Seveny percent of infectious bacteria are resistant to at least one commonly used antibiotic treatment (NIH). In the United States alone, 1.7 million people get an infection while in a hospital environment with just under 100,000 of these cases resulting in death (NIH). This situation demonstrates the increased need for the development of new antibiotic therapies. A rapid assay examining the binding affinity of novel aminoglycosides to the A-site and other nucleic acid sites will facilitate the discovery of effective therapies. In Phase I, we have developed a fluorescence based competition assay using a 27-base RNA model of the ribosomal A-site and a novel fluorescent reporter molecule, F-neo. This assay is readily adaptable to a high throughput format as larger compound libraries are established. In Phase II our specific aims are 1) develop an automated fluorescent based assay for screening broad based RNA targets. This aim includes expanding the current assay to a high throughput automated screen and adapting the assay to include other nucleic acid drug targets. 2) Expand the library of aminoglycoside conjugated molecules. Phase I resulting in a small in house compound library that was screened using the assay developed in Phase I. In Phase II the library will be greatly expanded by the conjugation of aminoglycosides with different classes of compounds using a variety of linker lengths and types. 3) Screening of NUBAD compounds to determine and characterize the activity. This in vivo assay will help establish a correlation between "hits" from the assay and activity in the cell. At the conclusion of this work, we will have established a commercially available assay for the high throughput screening of compounds that target nucleic acids. This technology will fill a niche in the high throughput screening industry, and result in more efficien development of compounds that treat disease related to nucleic acid therapies.
描述(由申请人提供):治疗疾病靶核酸的一些最重要的疗法。以核酸为靶点的药物包括抗癌药物、抗生素和
抗病毒药物。这些类别的药物在全球的年销售额合计约为 1,390 亿美元。在所有抗生素年销售额 420 亿美元中,针对核酸的抗生素占 145 亿美元,并且占前五类抗生素中的三类。抗生素耐药性危机造成了巨大的经济和生命损失。百分之七十的传染性细菌对至少一种常用抗生素治疗 (NIH) 具有耐药性。仅在美国,就有 170 万人在医院环境中受到感染,其中不到 10 万例导致死亡 (NIH)。这种情况表明对开发新抗生素疗法的需求不断增加。快速检测新型氨基糖苷类与 A 位点和其他核酸位点的结合亲和力将有助于发现有效的治疗方法。在第一阶段,我们开发了一种基于荧光的竞争测定法,使用核糖体 A 位点的 27 碱基 RNA 模型和新型荧光报告分子 F-neo。随着更大的化合物库的建立,该测定很容易适应高通量格式。在第二阶段,我们的具体目标是 1) 开发一种基于自动化荧光的检测方法,用于筛选广泛的 RNA 靶标。这一目标包括将当前的测定扩展到高通量自动筛选,并调整该测定以包括其他核酸药物靶标。 2) 扩展氨基糖苷结合分子库。第一阶段产生了一个小型内部化合物库,该库是使用第一阶段开发的测定法进行筛选的。在第二阶段,通过使用各种接头长度和类型将氨基糖苷类与不同类别的化合物缀合,该库将大大扩展。 3) 筛选 NUBAD 化合物以确定和表征活性。这种体内测定将有助于建立测定的“命中”与细胞活性之间的相关性。在这项工作结束时,我们将建立一种商业化的检测方法,用于高通量筛选靶向核酸的化合物。该技术将填补高通量筛选行业的空白,并导致更有效地开发治疗与核酸疗法相关的疾病的化合物。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Characterization of ribosomal binding and antibacterial activities using two orthogonal high-throughput screens.
使用两个正交高通量筛选表征核糖体结合和抗菌活性。
- DOI:10.1128/aac.00671-13
- 发表时间:2013
- 期刊:
- 影响因子:4.9
- 作者:King,Ada;Watkins,Derrick;Kumar,Sunil;Ranjan,Nihar;Gong,Changjun;Whitlock,Jarred;Arya,DevP
- 通讯作者:Arya,DevP
An assay for human telomeric G-quadruplex DNA binding drugs.
- DOI:10.1016/j.bmcl.2013.10.030
- 发表时间:2013-12-15
- 期刊:
- 影响因子:2.7
- 作者:Watkins, Derrick;Ranjan, Nihar;Kumar, Sunil;Gong, Changjun;Arya, Dev P.
- 通讯作者:Arya, Dev P.
Aminoglycoside Functionalization as a Tool for Targeting Nucleic Acids.
氨基糖苷功能化作为靶向核酸的工具。
- DOI:10.1007/978-1-4939-9216-4_9
- 发表时间:2019
- 期刊:
- 影响因子:0
- 作者:Watkins,Derrick;Maiti,Krishnagopal;Arya,DevP
- 通讯作者:Arya,DevP
{{
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 }}
DEV PRIYA ARYA其他文献
DEV PRIYA ARYA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('DEV PRIYA ARYA', 18)}}的其他基金
Delivery of chemically modified PNA oligomers
化学修饰的 PNA 寡聚物的递送
- 批准号:
10006671 - 财政年份:2020
- 资助金额:
$ 8.16万 - 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:
9891947 - 财政年份:2019
- 资助金额:
$ 8.16万 - 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:
$ 8.16万 - 项目类别:
Targeting RNA conformation for drug development
药物开发中的靶向 RNA 构象
- 批准号:
8252970 - 财政年份:2012
- 资助金额:
$ 8.16万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 8.16万 - 项目类别:
Research Grant