Targeting Tyrosine Phosphatases: Time to End the Stigma.
Targeting Tyrosine Phosphatases: Time to End the Stigma.
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DOI：
10.1016/j.tips.2017.03.004
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发表时间：
2017-06
影响因子：
13.8
通讯作者：
Bottini N
中科院分区：
文献类型：
--
作者：
Stanford SM;Bottini N
蛋白酪氨酸磷酸酶(PTPs)是许多细胞过程中必不可少的一类酶，已有几种PTPs被证实为人类疾病的治疗靶点。从历史上看，针对PTPs的药物的开发一直具有极大的挑战性，导致这些酶被污名化为无法下药的靶点。尽管存在这些困难，但给PTP下药的努力仍在继续，近年来出现了大量新的探针，为对新旧PTP靶标进行生物学检查提供了机会。在这里，我们将讨论在药物PTPs方面的进展，特别强调开发具有生物活性的选择性探针。我们将描述新的小分子正构体、变构和寡聚PTP抑制剂的发展，并讨论针对受体PTP亚家族的生物制剂的新研究。
Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for numerous cellular processes, and several PTPs have been validated as therapeutic targets for human diseases. Historically, development of drugs targeting PTPs has been highly challenging, leading to stigmatization of these enzymes as undruggable targets. Despite these difficulties, efforts to drug PTPs have persisted, and recent years have seen an influx of new probes, providing opportunities for biological examination of old and new PTP targets. Here we will discuss progress towards drugging PTPs, with special emphasis on development of selective probes with biological activity. We will describe development of new small-molecule orthosteric, allosteric and oligomerization PTP inhibitors, and discuss new studies targeting the receptor PTP subfamily with biologics.