Explorative studies of novel IgE ligands

新型 IgE 配体的探索性研究

基本信息

批准号：
10055790
负责人：
Theodore S Jardetzky
金额：
$ 23.66万
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 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10055790
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. !

项目摘要大多数过敏反应是由特定于过敏原的免疫球蛋白E（IgE）抗体引起的触发肥大细胞和嗜碱性介导的潜在炎症反应。 IgE与高亲和力结合在这些过敏性效应细胞上表达的受体（FCεRI），使其成为共同的中心相互作用不同过敏原的反应。抗IgE抗体（Omalizumab）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的可行性：FcεRI相互作用治疗益处。我们已经开发了多种方法来识别IgE的小分子配体并确定了诺言的潜在客户进行进一步研究。在此提案中，我们将进一步调查这些导致探索产生新型探针的IgE功能和抑制的可能性。呢