Explorative studies of novel IgE ligands

新型 IgE 配体的探索性研究

基本信息

批准号：
10194357
负责人：
Theodore S Jardetzky
金额：
$ 19.71万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-16 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10194357
关键词：
Aerosols Affinity Allergens Allergic Allergic Reaction Antibodies Basophils Binding Binding Sites Biochemical Biological Assay Biophysics Cells Chemical Structure Chemicals Chronic Collaborations Complex Crystallization Data Detection Development Diagnostic Docking Dose Effector Cell Extrinsic asthma Family Fc Receptor Food Hypersensitivity Foundations Goals Head Hot Spot Hypersensitivity IgE IgE Receptors Inflammatory Response Injections Knowledge Laboratories Libraries Ligands Maps Mediating Methods Molecular Conformation Oral Pharmaceutical Chemistry Play Protein Fragment Proteins Receptor Inhibition Research Role Site Structure Surface Surface Plasmon Resonance Symptoms Synthesis Chemistry Therapeutic Therapeutic Uses Therapeutic antibodies Urticaria allergic response analog base clinical candidate drug discovery experimental study falls functional group improved inhibitor/antagonist insight lead candidate lead series mast cell novel novel therapeutics omalizumab protein protein interaction receptor receptor binding response scaffold screening small molecule small molecule inhibitor therapeutic target

项目摘要

Project Summary Most allergic reactions are caused by immunoglobulin E (IgE) antibodies that are specific for allergens and that trigger potent inflammatory responses mediated by mast cells and basophils. IgE binds to the high affinity receptor (FcεRI) expressed on these allergic effector cells, making this a central interaction that is common to different allergen-specific responses. The anti-IgE antibody (omalizumab) is currently used to treat allergic asthma and chronic idiopathic urticaria, demonstrating the feasibility of inhibiting the IgE:FcεRI interaction for therapeutic benefit. We have developed multiple approaches to identifying small molecule ligands for the IgE and identified promising leads for further studies. In this proposal, we will further investigate these leads to explore the possibility of producing novel probes for IgE function and inhibition. !

项目概要大多数过敏反应是由对过敏原具有特异性的免疫球蛋白 E (IgE) 抗体引起的触发由肥大细胞和嗜碱性粒细胞介导的强效炎症反应。受体 (FcεRI) 在这些过敏效应细胞上表达，使其成为过敏反应中常见的核心相互作用不同的过敏原特异性反应抗 IgE 抗体（奥马珠单抗）目前用于治疗过敏。哮喘和慢性特发性荨麻疹，证明了抑制 IgE:FcεRI 相互作用的可行性我们开发了多种治疗方法来识别 IgE 的小分子配体。并确定了有希望进一步研究的线索。在本提案中，我们将进一步研究这些线索。探索生产 IgE 功能和抑制的新型探针的可能性。！