Tec inhibitors- A new therapeutic for allergic diseases

Tec抑制剂——过敏性疾病的新疗法

• 批准号: 6443542
• 负责人: Yuko Kawakami
• 金额: $ 23.36万
• 依托单位: ALLIMMUNE, LLC
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6443542
• 关键词: antibody receptor; antiinflammatory agents; atopic dermatitis; drug screening /evaluation; enzyme inhibitors; hypersensitivity; laboratory mouse; leukocyte activation /transformation; protein tyrosine kinase; quinones

DESCRIPTION (provided by applicant): The incidence of allergic diseases such as atopic dermatitis (AD) has been dramatically increasing in the US and other industrialized countries for the past two decades. We and others have demonstrated that Tec family protein-tyrosine kinases have crucial roles in the activation of immune cells elicited by the engagement of antigen receptors or Fc receptors. As such, these kinases are supposed to play critical roles in the pathogenesis of AD and other allergic diseases that involve the activation of T and B lymphocytes, mast cells, and eosinophils. We recently identified a small-molecule compound, terreic acid (TA), as a selective inhibitor of Tec family kinases. In addition, we recently established highly efficient experimental conditions to rapidly induce skin lesions in AD-prone NC/Nga mice. Using this mouse model, we propose to explore whether TA or related compounds are therapeutically efficacious as a treatment of AD. Since we have a screening method for searching for Tec inhibitors whose usefulness has been proven, we will also expand our search for better compounds.

描述(申请人提供)：过敏性疾病的发病率 特应性皮炎(AD)在美国和其他国家急剧增加 在过去的二十年里，工业化国家已经取得了巨大的进步。我们和其他人有 研究表明，Tec家族蛋白酪氨酸激酶在 通过抗原受体的结合或结合引起的免疫细胞的激活 Fc受体。因此，这些激酶被认为在 阿尔茨海默病和其他涉及T细胞激活的过敏性疾病的发病机制 B淋巴细胞、肥大细胞和嗜酸性粒细胞。我们最近发现了一种 作为Tec选择性抑制剂的小分子化合物土酸(TA) 家族肌动蛋白。此外，我们最近建立了高效的 快速诱导AD倾向的NC/NGA小鼠皮肤病变的实验条件。 利用这一小鼠模型，我们建议探索TA或相关化合物 是一种治疗阿尔茨海默病的有效药物。因为我们有放映 寻找有效的Tec抑制剂的方法，我们 也将扩大我们对更好化合物的搜索。