Explorative studies of novel IgE ligands

新型 IgE 配体的探索性研究

• 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
• 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

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免疫球蛋白E(IgE)抗体引起的，这种抗体是针对过敏原的 触发由肥大细胞和嗜碱性粒细胞介导的强烈炎症反应。免疫球蛋白与高亲和力结合 受体(FcεRI)在这些过敏效应细胞上表达，使这一共同的中枢相互作用 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，证明抑制Ig E：FcεRI相互作用的可行性 治疗效果。我们已经开发了多种方法来识别IgE的小分子配体 并为进一步研究确定了有希望的线索。在这项建议中，我们将进一步调查这些线索，以 探索生产新的免疫球蛋白E功能和抑制探针的可能性。 好了！