Strategies to Target ADAM17 in Disease: From its Discovery to the iRhom Revolution.
Strategies to Target ADAM17 in Disease: From its Discovery to the iRhom Revolution.
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DOI：
10.3390/molecules26040944
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发表时间：
2021-02-10
期刊：
影响因子：
--
通讯作者：
Scilabra SD
中科院分区：
文献类型：
--
作者：
Calligaris M;Cuffaro D;Bonelli S;Spanò DP;Rossello A;Nuti E;Scilabra SD
几十年来，崩解素和金属蛋白酶17 （ADAM17）一直是深入研究的对象。自从作为肿瘤坏死因子转化酶被发现以来，它一直被认为是一个主要的药物靶点，特别是在炎症性疾病和癌症的背景下。然而，开发针对ADAM17的药物比预期的要困难。这通常是由于其多功能性，ADAM17可以释放除肿瘤坏死因子α (TNF)外的80多种不同的跨膜蛋白，并且其结构与其他金属蛋白酶相似。这篇综述综述了ADAM17在疾病中的不同作用，以及在许多病理状态的体内模型中其消融的影响。此外，本文全面涵盖了已经开发的实现ADAM17选择性抑制的方法，从最新的非锌结合的ADAM17合成抑制剂到利用iRhom2特异性靶向免疫细胞中的ADAM17。
For decades, disintegrin and metalloproteinase 17 (ADAM17) has been the object of deep investigation. Since its discovery as the tumor necrosis factor convertase, it has been considered a major drug target, especially in the context of inflammatory diseases and cancer. Nevertheless, the development of drugs targeting ADAM17 has been harder than expected. This has generally been due to its multifunctionality, with over 80 different transmembrane proteins other than tumor necrosis factor α (TNF) being released by ADAM17, and its structural similarity to other metalloproteinases. This review provides an overview of the different roles of ADAM17 in disease and the effects of its ablation in a number of in vivo models of pathological conditions. Furthermore, here, we comprehensively encompass the approaches that have been developed to accomplish ADAM17 selective inhibition, from the newest non-zinc-binding ADAM17 synthetic inhibitors to the exploitation of iRhom2 to specifically target ADAM17 in immune cells.
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影响因子：
8
作者：
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影响因子：
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