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二聚化的翻译调控肿瘤蛋白(一种组胺释放因子)的抑制剂可作为抗过敏药物候选物。

Inhibitors of dimerized translationally controlled tumor protein, a histamine releasing factor, may serve as anti-allergic drug candidates.

作者信息

Maeng Jeehye, Lee Kyunglim

机构信息

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.

出版信息

Biochimie. 2023 Aug;211:141-152. doi: 10.1016/j.biochi.2023.03.011. Epub 2023 Mar 22.

Abstract

It has been established that translationally controlled tumor protein (TCTP), also called histamine releasing factor (HRF), exhibits cytokine-like activities associated with initiation of allergic responses only after forming dimers (dTCTP). Agents that inhibit dTCTP by preventing its dimerization or otherwise block its function, also block development of allergic reactions, thereby serving as potential drugs to treat allergic diseases. Several lines of evidence have proven that peptides and antibodies that specifically inhibit the interactions between dTCTP and either its putative receptor or immunoglobulins exhibit significant in vivo efficacy as potential anti-inflammatory agents in murine models of allergic inflammatory diseases. This review highlights the development of several inhibitors targeting dTCTP and discusses how they affect the pathophysiological processes of allergic and inflammatory diseases in several animal models and offers new perspectives on anti-allergic drug discovery.

摘要

已经确定,翻译控制肿瘤蛋白(TCTP),也称为组胺释放因子(HRF),仅在形成二聚体(dTCTP)后才表现出与过敏反应起始相关的细胞因子样活性。通过阻止dTCTP二聚化或通过其他方式阻断其功能来抑制dTCTP的药物,也能阻断过敏反应的发展,从而成为治疗过敏性疾病的潜在药物。多项证据表明,特异性抑制dTCTP与其假定受体或免疫球蛋白之间相互作用的肽和抗体,在过敏性炎症疾病的小鼠模型中作为潜在的抗炎剂具有显著的体内疗效。本综述重点介绍了几种靶向dTCTP的抑制剂的开发,并讨论了它们如何影响几种动物模型中过敏性和炎症性疾病的病理生理过程,为抗过敏药物发现提供了新的视角。

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