Discovery of inhibitors that target HBx for the treatment of chronic HBV infection
Discovery of inhibitors that target HBx for the treatment of chronic HBV infection
批准号:
10155986
负责人:
Glen Andrew Coburn
金额:
$25.28万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-12-15 至 2022-11-30
关键词:
AcuteAdultAlanine TransaminaseAntibodiesAntiviral AgentsAutomobile DrivingBindingBiological AssayChromosomesChronicChronic Hepatitis BCirrhosisCollaborationsComplexDNA biosynthesisDNA-Binding ProteinsDevelopmentDisease ProgressionDoseDrug KineticsDrug TargetingEvaluationExhibitsFeasibility StudiesFundingGene ExpressionGene SilencingGenetic TranscriptionGoalsHepatitisHepatitis BHepatitis B Surface AntigensHepatitis B VirusHepatitis B X-ProteinHepatocyteHistologicHost Defense MechanismHumanImmuneIndividualInfectionIntegration Host FactorsInterferon-alphaInvestigationLeadLibrariesLifeLiverLiver CirrhosisLiver diseasesLuciferasesMaintenanceMolecular TargetOralPathway interactionsPerinatal ExposurePersonsPharmaceutical ChemistryPharmaceutical PreparationsPhasePlayPrimary carcinoma of the liver cellsPropertyPublishingReverse Transcriptase InhibitorsRiskRoleSeriesSignal TransductionSmall Business Innovation Research GrantStructure-Activity RelationshipSystemTechnologyTenofovirTestingUV induced DNA damageUbiquitinationVaccinesVertical Disease TransmissionViralViral GenesViral Regulatory ProteinsVirus DiseasesVirus InhibitorsVirus Replicationanalogcandidate selectioncounterscreencytotoxicitydrug discoveryearly childhoodentecavirextrachromosomal DNAhigh throughput screeningimmunoregulationimprovedindexinginhibitor/antagonistlead optimizationlead seriesnovelpreventprogramsrecruitresponseseroconversionsmall moleculesmall molecule librariessuccessubiquitin-protein ligaseviral DNA
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
The HBV X protein (HBx) represents an attractive target for drug discovery efforts as it plays a central role in
activating viral gene expression and promoting conditions that allow the cccDNA form of HBV to persist in the
hepatocytes of chronically infected individuals. The objective of this Phase I SBIR feasibility study is to identify
drug-like compounds that selectively inhibit a key interaction between HBx and a host factor DDB1 (UV
damaged DNA binding protein 1) that is responsible for activating transcription from the cccDNA template.
During the course of this Phase I funding period, we will execute a hit finding campaign against a library of
200,000 compounds with optimal drug-like properties. Quality hits that emerge from the assay will be subjected
to follow-on testing that will investigate the potency, selectivity, and mechanism of action. The most interesting
of these compounds will be subjected to medicinal chemistry driven hit-to-lead to explore structure-activity
relationships (SAR). The overall goal of this project is to discover one or more novel lead series which is
defined as a chemotype inhibitor that demonstrates tractable SAR, potent antiviral activity against HBV and
minimal cytotoxicity. Success in these endeavors will trigger the submission of a Phase II application that will
advance the program from Early Lead Optimization through to Candidate Selection.
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依托单位:
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依托单位:
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依托单位:
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依托单位:
海外基金