Tec inhibitors- A new therapeutic for allergic diseases

Tec抑制剂——过敏性疾病的新疗法

• 批准号: 6608039
• 负责人: Yuko Kawakami
• 金额: $ 20.98万
• 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/6608039
• 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（由申请人提供）：过敏性疾病的发生率，如 特应性皮炎（AD）在美国和其他国家急剧增加， 工业化国家近20年来我们和其他人已经 表明Tec家族蛋白酪氨酸激酶在细胞凋亡中起着至关重要的作用。 通过抗原受体的接合引起的免疫细胞的活化，或 Fc受体。因此，这些激酶被认为在肿瘤的发生中起关键作用。 AD和其他涉及T细胞活化的过敏性疾病的发病机制 以及B淋巴细胞、肥大细胞和嗜酸性粒细胞。我们最近发现了一个 小分子化合物土酸（TA）作为Tec选择性抑制剂 家族激酶此外，我们最近建立了高效的 在实验条件下快速诱导AD易感性NC/Nga小鼠的皮肤损伤。 使用这种小鼠模型，我们建议探索TA或相关化合物是否 在治疗AD方面是有效的。因为我们有一个筛选 方法寻找Tec抑制剂的有效性已被证明，我们 也将扩大我们对更好化合物的研究。

项目成果

An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases.

• DOI: 10.2332/allergolint.o-07-486
• 发表时间: 2007-12-01
• 期刊: Allergology international : official journal of the Japanese Society of Allergology
• 作者: Kawakami, Yuko;Yumoto, Kenji;Kawakami, Toshiaki
• 通讯作者: Kawakami, Toshiaki