Core B: Discovery Core
核心B:发现核心
基本信息
- 批准号:10513681
- 负责人:
- 金额:$ 938.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-16 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:Antiviral AgentsBindingBinding SitesBiological AssayBiologyBiophysicsBromodomainCaspaseChemicalsCommunitiesComplementComputing MethodologiesDNADNA-Directed RNA PolymeraseDataDevelopmentDiamondDrug TargetingEnzymatic BiochemistryEnzymesFamilyGenerationsHumanIndustrializationLeadLibrariesLigandsLightMethodologyMethyltransferaseMolecular TargetPharmaceutical ChemistryPharmacologyPhaseProbabilityProtein Binding DomainProtein FamilyProteinsRNA HelicaseRecombinant ProteinsRecombinantsScientistSerine ProteaseSiteSourceStructureStructure-Activity RelationshipTechnologyTertiary Protein StructureTrustValidationViralViral PhysiologyVirusWD RepeatWorkX-Ray Crystallographyantiviral drug developmentassay developmentbaseclinical candidatedeep learningdesigndrug candidatedrug discoveryexperienceinnovationknowledge baselead optimizationlearning strategynew therapeutic targetnovelopen datapandemic diseaseprogramsprotein expressionscreeningstructural genomicstool
项目摘要
ABSTRACT
The READDI AViDD Center (READDI-AC) will create new broad spectrum direct acting antiviral (DAA) drug
candidates to treat current and emerging pandemic threats. Discovery Core B will serve as the discovery
engine for identification of new inhibitory chemical matter (hits), validation of chemically tractable molecular
target sites, and will support the optimization of hits to pharmacological tools (chemical probes) and Leads by
MedChem Core D. Together and also with Projects 2-5 and Enzymology Core C, we will feed a pipeline of
Lead compounds to the Project teams and industrial partners to complement existing assets.
This proposal brings a world-leading team, all affiliated with, or collaborators of, the Structural Genomics
Consortium (SGC). The SGC is an open science partnership that supports the pharmacological identification of
new drug targets and is a world leader in the generation, characterization, and distribution of high-quality
chemical probes – one of the most impactful tools for target validation, and an important early milestone in drug
discovery. The SGC uses a protein family (aka target class) approach to drive efficiency in development of
chemical probes. Through our strong experience with open science and protein family chemical probe
development, Discovery Core B together with MedChem Core D are poised to tackle the READDI-AC portfolio
of targets, which spans three main families of viral enzymes: RNA polymerases, RNA helicases, and
cysteine and serine proteases.
Discovery Core B aims to prime the READI-AC and global DAA drug discovery pipeline by generating high-
quality chemical probes that will accelerate the development of innovative direct acting anti-viral drugs.
Aim 1. Portfolio creation: The Discovery Core B will work closely with the Enzymology Core C, MedChem
Core D and Projects 2-5 to select a portfolio of tractable DAA target sites across the four virus families and
three main enzyme target protein families, such that eight target sites enter the hit discovery phase each year.
Aim 2. Hit discovery and Validation: The Discovery Core B will use both diversity- and knowledge-based
HTS for hit discovery using purified recombinant enzyme in one or more of >10 assay formats. Hits will be
validated though a robust workflow to yield a data package (Hit CV) for consideration for further optimization.
Aim 3. Hit-to-Probe (H2P) activities. Discovery Core B will support MedChem Core D with rapid execution
of assays and X-ray crystallography to support structure-guided SAR of compounds made and/or designed in
MedChem Core D. We will also evaluate viral-active compounds for selectivity against related human enzymes.
Discovery Core B will deliver at least 12 high-quality Hit CVs every year, for consideration by Adman Core A
as starting points for Hit-to-Probe/Lead optimization, and support the Hit-to-Probe activities by the Projects. All
chemical probes will be made openly available to the scientific community for use as pharmacological tools.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Kenneth Hugh Pearce其他文献
Kenneth Hugh Pearce的其他文献
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{{ truncateString('Kenneth Hugh Pearce', 18)}}的其他基金
Discovery of allosteric activators of phospholipase C-gamma2 to treat Alzheimer's disease
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- 批准号:
10901007 - 财政年份:2023
- 资助金额:
$ 938.18万 - 项目类别:
A high-throughput platform to identify selective allosteric inhibitors of the PLC-y isozymes
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10399533 - 财政年份:2021
- 资助金额:
$ 938.18万 - 项目类别:
A high-throughput platform to identify selective allosteric inhibitors of the PLC-y isozymes
用于鉴定 PLC-y 同工酶选择性变构抑制剂的高通量平台
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10185322 - 财政年份:2021
- 资助金额:
$ 938.18万 - 项目类别:
A high-throughput platform to identify selective allosteric inhibitors of the PLC-y isozymes
用于鉴定 PLC-y 同工酶选择性变构抑制剂的高通量平台
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- 资助金额:
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10530649 - 财政年份:2019
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10132267 - 财政年份:2019
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$ 938.18万 - 项目类别:
Establishing MAGE-A4/RAD18 as a novel cancer-specific chemotherapeutic target
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10596489 - 财政年份:2019
- 资助金额:
$ 938.18万 - 项目类别:
Establishing MAGE-A4/RAD18 as a novel cancer-specific chemotherapeutic target
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9905492 - 财政年份:2019
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$ 938.18万 - 项目类别:
Establishing MAGE-A4/RAD18 as a novel cancer-specific chemotherapeutic target
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10363652 - 财政年份:2019
- 资助金额:
$ 938.18万 - 项目类别:
Pathological Reprogramming of DNA Damage Signaling in Neoplastic Cells
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- 批准号:
10301006 - 财政年份:2019
- 资助金额:
$ 938.18万 - 项目类别:
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