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Design of Aminopeptidase N Inhibitors as Anti-cancer Agents
Journal of Medicinal Chemistry ( IF 7.3 ) Pub Date : 2018-04-09 00:00:00 , DOI: 10.1021/acs.jmedchem.7b00782
Sk. Abdul Amin 1 , Nilanjan Adhikari 1 , Tarun Jha 1
Affiliation  

Aminopeptidase N (APN) is an important metalloenzyme. It regulates multivariate cellular functions by different mechanisms such as enzymatic cleavage of peptides. This may play a role in endocytosis and regulate signal transduction. APN, a member of the M1 zinc metallopeptidase family, plays crucial roles in a variety of functions such as migration and invasion, and angiogenesis and metastasis of tumor cells. Therefore, APN inhibitors may be useful for the treatment of cancer. In this Perspective, structure–activity relationships of APN inhibitors are discussed to get an idea of possible lead candidates. APN inhibitors should possess an aryl hydrophobic function along with a zinc binding group attached to the hydrophobic group(s) to achieve high potency. This and other design aspects of APN inhibitors are discussed in this Perspective.

中文翻译:

氨基肽酶N抑制剂作为抗癌药的设计

氨肽酶N(APN)是一种重要的金属酶。它通过不同的机制(例如肽的酶切)调节多元细胞功能。这可能在胞吞作用和调节信号转导中起作用。APN是M1锌金属肽酶家族的成员,在多种功能(例如迁移和侵袭以及肿瘤细胞的血管生成和转移)中起着至关重要的作用。因此,APN抑制剂可用于治疗癌症。在此观点中,讨论了APN抑制剂的构效关系,以了解可能的潜在候选对象。APN抑制剂应具有芳基疏水功能以及与疏水基团相连的锌结合基团,以实现较高的效力。在此“观点”中讨论了APN抑制剂的这一方面和其他设计方面。
更新日期:2018-04-09
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