Small-Molecule Inhibitors of Necroptosis: Current Status and Perspectives.,Journal of Medicinal Chemistry

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Small-Molecule Inhibitors of Necroptosis: Current Status and Perspectives.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2019-10-31 , DOI: 10.1021/acs.jmedchem.9b01317
Chunlin Zhuang _{1,

2} , Fener Chen _{1,

2}

Affiliation

Necroptosis, an important form of programmed cell death (PCD), is a highly regulated caspase-independent type of cell death that plays a critical role in the pathophysiology of various inflammatory, infectious, and degenerative diseases. Currently, receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) have been widely recognized as critical therapeutic targets of the necroptotic machinery. Targeting RIPK1, RIPK3, and/or MLKL is a promising strategy for necroptosis-related diseases. Following the identification of the first RIPK1 inhibitor Nec-1 in 2005, the antinecroptosis field is attracting increasing research interest from multiple disciplines, including the biological and medicinal chemistry communities. Herein, we will review the functions of necroptosis in human diseases, as well as the related targets and representative small-molecule inhibitors, mainly focusing on research articles published during the past 10 years. Outlooks and perspectives on the associated challenges are also discussed.

中文翻译：

坏死性小分子抑制剂：现状与展望。

坏死病是程序性细胞死亡（PCD）的一种重要形式，是高度调控的caspase依赖性细胞死亡类型，在各种炎症，传染性和退行性疾病的病理生理中起着至关重要的作用。当前，受体相互作用蛋白激酶1（RIPK1），RIPK3和混合谱系激酶结构域样蛋白（MLKL）已被广泛认为是坏死性机器的关键治疗靶标。靶向RIPK1，RIPK3和/或MLKL是与坏死病相关疾病的一种有前途的策略。在2005年识别出第一个RIPK1抑制剂Nec-1之后，抗肿瘤的领域吸引了来自多个学科的越来越多的研究兴趣，包括生物学和药物化学界。在这里，我们将回顾坏死病在人类疾病中的功能，以及相关靶标和代表性小分子抑制剂，主要侧重于过去10年中发表的研究文章。还讨论了相关挑战的前景和观点。

更新日期：2019-11-01

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