Developing A Platform Technology For β-Cell-Targeted Drug Delivery
开发β细胞靶向药物输送的平台技术
基本信息
- 批准号:10729390
- 负责人:
- 金额:$ 55.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AntibodiesAutonomous ReplicationBeta CellBiochemicalBiologicalBiological AssayBiologyCell LineageCell Membrane PermeabilityCell ProliferationCell membraneCell surfaceCellsCellular AssayChemicalsCoculture TechniquesDataDaughterDependenceDiabetes MellitusDiabetic mouseDoseDrug Delivery SystemsDrug KineticsDrug TargetingEndosomesEnsureFunctional disorderGenerationsGoalsHistologyHumanHuman Cell LineImpairmentIn VitroInsulinInsulin-Dependent Diabetes MellitusIslets of Langerhans TransplantationLeadMeasuresMediatingMembraneMethodsModelingMolecularMusNatural regenerationNeuroendocrine CellPathologicPharmaceutical ChemistryPharmaceutical PreparationsPre-Clinical ModelProdrugsProductionProtein IsoformsRecombinantsSecretory VesiclesSpecificityStructure-Activity RelationshipTechnologyTherapeuticTissuesTransplantationTreatment EfficacyWorkbiophysical propertiesblood glucose regulationcell typecellular targetingdesignextracellularglucose tolerancegrowth promoting activityhumanized mousein vivoinnovationisletnext generationnovelpeptidylglycine alpha-amidating monooxygenasepharmacologicpre-clinicalpreventregenerativeregenerative therapyregenerative treatmentrestorationscreeningsmall moleculesuccesstargeted deliverytargeted treatmenttechnology platformtrafficking
项目摘要
PROJECT SUMMARY
Type 1 diabetes is characterized by the loss of β-cell mass and decreased insulin production capacity. Thus,
developing a pharmacologic method for stimulating the expansion of β-cell mass has substantial potential
therapeutic value. Recently, our group and others have successfully developed highly potent small-molecule
inducers of human β-cell proliferation; however, the growth-promoting activity of these molecules is non-
selective. Consequently, the potential for inducing off-target cellular proliferation is a primary barrier to the safe
use of these regenerative compounds in humans. Herein, a novel, generalizable prodrug strategy for the
selective delivery of regerative therapeutics to the β-cell will be developed. The strategy leverages a unique
biologic activity of the β-cell to convert latent prodrugs into bioactive daughter compounds. Building on prior
success, progress will be furthered by incorporating relevant advances made in the broader field of targeted drug
delivery into this new prodrug strategy; including the incorporation of molecular linkers used in antibody- and
small molecule-drug conjugates that ensure compounds are fully latent prior to bioactivation and are unscarred
following bioactivation. Additionally, the cellular mechanisms of prodrug activation will be elucidated. This work
will deliver a robust, milestone-based data package for β-cell targeted drug delivery that includes a deep
understanding of prodrug bioactivation, structure-activity relationship data, pharmacokinetic characterization,
cell-type-specific activity and in vivo efficacy with a human islet-based preclinical model. The replicative activity
of target (β-cells) and off-target tissues will be assessed following short-term and long-term compound exposure;
studies critical to demonstrating the sustained specificity and efficacy of this β-cell targeted therapeutic delivery
strategy. These studies have the potential to deliver safe, potentially transformative, first-in-class lead
compounds for regenerative treatment of diabetes. Critically, the developed technology may be used for β-cell-
targeted delivery of nearly any therapeutic.
项目总结
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Justin Pierce Annes其他文献
Justin Pierce Annes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('Justin Pierce Annes', 18)}}的其他基金
Development of Beta-Cell-Targeted Regenerative Therapeutics Using A Novel Prodrug Strategy
使用新型前药策略开发β细胞靶向再生疗法
- 批准号:
10215497 - 财政年份:2019
- 资助金额:
$ 55.62万 - 项目类别:
Development of Beta-Cell-Targeted Regenerative Therapeutics Using A Novel Prodrug Strategy
使用新型前药策略开发β细胞靶向再生疗法
- 批准号:
10661006 - 财政年份:2019
- 资助金额:
$ 55.62万 - 项目类别:
Development of Beta-Cell-Targeted Regenerative Therapeutics Using A Novel Prodrug Strategy
使用新型前药策略开发β细胞靶向再生疗法
- 批准号:
10453575 - 财政年份:2019
- 资助金额:
$ 55.62万 - 项目类别:
Leveraging the Uniquely High Beta-Cell Zinc Content for Targeted Drug Delivery
利用独特的高β细胞锌含量进行靶向药物输送
- 批准号:
10207073 - 财政年份:2015
- 资助金额:
$ 55.62万 - 项目类别:
Leveraging the Uniquely High Beta-Cell Zinc Content for Targeted Drug Delivery
利用独特的高β细胞锌含量进行靶向药物输送
- 批准号:
10576401 - 财政年份:2015
- 资助金额:
$ 55.62万 - 项目类别:
Leveraging the Uniquely High Beta-Cell Zinc Content for Targeted Drug Delivery
利用独特的高β细胞锌含量进行靶向药物输送
- 批准号:
10366072 - 财政年份:2015
- 资助金额:
$ 55.62万 - 项目类别:
The Role of Adenosine Kinase in Controlling Beta-Cell Regeneration
腺苷激酶在控制 β 细胞再生中的作用
- 批准号:
8888112 - 财政年份:2015
- 资助金额:
$ 55.62万 - 项目类别:
Interrogating the Role of Adenosine Kinase in Islet Beta-Cells
探讨腺苷激酶在胰岛β细胞中的作用
- 批准号:
8480250 - 财政年份:2013
- 资助金额:
$ 55.62万 - 项目类别:
Interrogating the Role of Adenosine Kinase in Islet Beta-Cells
探讨腺苷激酶在胰岛β细胞中的作用
- 批准号:
8643226 - 财政年份:2013
- 资助金额:
$ 55.62万 - 项目类别:














{{item.name}}会员




