Preclinical development of capsid assembly modulators for the treatment of chronic hepatitis B virus infection
用于治疗慢性乙型肝炎病毒感染的衣壳组装调节剂的临床前开发
基本信息
- 批准号:10612081
- 负责人:
- 金额:$ 100万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-24 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcuteAdultAlanine TransaminaseAntibodiesAntiviral AgentsCapsidCell Culture TechniquesCharacteristicsChronicChronic Hepatitis BCirrhosisCore ProteinDNA biosynthesisDataDevelopmentDisease ProgressionDoseDrug DesignDrug KineticsEvaluationExhibitsGene SilencingGeneticGenotypeGoalsHBV GenotypeHepatitisHepatitis B InfectionHepatitis B Surface AntigensHepatitis B VirusHepatocyteHistologicHumanImmuneIn VitroIndividualInfectionInvestigationInvestigational DrugsInvestigational New Drug ApplicationLeadLife Cycle StagesLiver CirrhosisLiver diseasesMacaca fascicularisMalignant neoplasm of liverMaximum Tolerated DoseMusPatientsPegylated Interferon AlfaPerinatal ExposurePersonsPharmacodynamicsPharmacologyPharmacology StudyPhasePhase I Clinical TrialsPolymerasePreparationPrimary carcinoma of the liver cellsPropertyPublic HealthRattusRegimenReportingResistance profileReverse Transcriptase InhibitorsRiskRodentSafetySeriesSmall Business Innovation Research GrantStructureTenofovirTestingToxic effectToxicokineticsToxicologyVaccinesVertical TransmissionViralViral PhysiologyVirus DiseasesVirus Replicationanalogearly childhoodentecavirexperiencefirst-in-humanhealthy volunteerimmune modulating agentsimmunomodulatory therapiesimmunoregulationimprovedmouse modelnovelpre-clinicalpreclinical developmentpreventprogramsprogression riskresearch clinical testingscale upscreeningseroconversionsuccesstreatment responseviral DNA
项目摘要
PROJECT SUMMARY
Despite the availability of a safe and effective vaccine, there remains over 257 million people chronically
infected with hepatitis B virus (HBV) world-wide. Individuals with chronic HBV infections are at risk for
complications due to liver disease and liver cancer. Chronic HBV is currently managed with nucleos(t)ide
reverse transcriptase inhibitors (NrtI) which partly suppress HBV DNA replication, normalize alanine
aminotransferase levels (ALT) and slow disease progression. Front-line therapies, however, are not curative
and patients with chronic HBV exhibit poor off-treatment responses requiring life-long therapy. New antivirals
and immunomodulatory approaches are, therefore, needed to further suppress viral replication and provide the
conditions that are required for immune control known as a “functional cure”. One of the most promising
classes of compounds under investigation are the core protein allosteric modulators (CpAM) that block HBV
replication at multiple stages of the viral life-cycle. Here, we report on a best-in-class CpAM that exhibits potent
pan-genotypic antiviral activity. In this project, we propose to advance our lead CpAM into definitive INDenabling studies to ready the compound for Phase 1 clinical trials in healthy volunteers and chronic HBV
patients. Combination regimens that include a CpAM, antivirals possessing distinct mechanisms of action
and/or novel immunomodulatory agents will be evaluated in a mouse model of HBV infection in preparation for
Phase 2 development in chronic HBV patienst.
项目总结
尽管有安全有效的疫苗可用,但仍有超过2.57亿人患有慢性病
在世界范围内感染了乙肝病毒(乙肝)。慢性乙肝病毒感染者有可能患上
因肝病和肝癌引起的并发症。慢性乙肝目前用核素(T)来管理。
逆转录酶抑制剂(NRTI)部分抑制HBVDNA复制,使丙氨酸正常化
转氨酶水平(ALT)和延缓疾病进展。然而,一线治疗并不能治愈
慢性乙肝患者表现出较差的停药反应,需要终身治疗。新型抗病毒药物
因此,需要免疫调节方法来进一步抑制病毒复制,并提供
免疫控制所需的条件被称为“功能治愈”。其中最有希望的是
研究中的一类化合物是阻断乙肝病毒的核心蛋白变构调节剂(CPAM)
在病毒生命周期的多个阶段复制。在这里,我们报告了一种同类中最好的CPAM,它展示了强大的
泛基因型抗病毒活性。在这个项目中,我们建议将我们的主导CPAM推进到确凿的非禁用研究中,为该化合物在健康志愿者和慢性乙肝患者中进行第一阶段临床试验做准备。
病人。包括CPAM的联合方案,具有不同作用机制的抗病毒药物
和/或新的免疫调节剂将在乙肝病毒感染的小鼠模型中进行评估,以准备
慢性乙肝患者的第二阶段进展。
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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Glen Andrew Coburn其他文献
Glen Andrew Coburn的其他文献
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{{ truncateString('Glen Andrew Coburn', 18)}}的其他基金
Discovery of antiviral inhibitors for the treatment of orthopoxvirus infections
发现治疗正痘病毒感染的抗病毒抑制剂
- 批准号:
10761185 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Optimization of orally bioavailable inhibitors for the treatment of COVID-19 and other human coronavirus infections
用于治疗 COVID-19 和其他人类冠状病毒感染的口服生物可利用抑制剂的优化
- 批准号:
10698831 - 财政年份:2023
- 资助金额:
$ 100万 - 项目类别:
Preclinical development of capsid assembly modulators for the treatment of chronic hepatitis B virus infection
用于治疗慢性乙型肝炎病毒感染的衣壳组装调节剂的临床前开发
- 批准号:
10257695 - 财政年份:2021
- 资助金额:
$ 100万 - 项目类别:
Preclinical development of capsid assembly modulators for the treatment of chronic hepatitis B virus infection
用于治疗慢性乙型肝炎病毒感染的衣壳组装调节剂的临床前开发
- 批准号:
10408826 - 财政年份:2021
- 资助金额:
$ 100万 - 项目类别:
Discovery of inhibitors that target HBx for the treatment of chronic HBV infection
发现针对 HBx 的抑制剂用于治疗慢性 HBV 感染
- 批准号:
10319178 - 财政年份:2020
- 资助金额:
$ 100万 - 项目类别:
Discovery of antiviral inhibitors of Ebola virus replication
发现埃博拉病毒复制的抗病毒抑制剂
- 批准号:
10216627 - 财政年份:2020
- 资助金额:
$ 100万 - 项目类别:
Discovery of inhibitors that target HBx for the treatment of chronic HBV infection
发现针对 HBx 的抑制剂用于治疗慢性 HBV 感染
- 批准号:
10155986 - 财政年份:2020
- 资助金额:
$ 100万 - 项目类别:
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