Small Molecules Targeting Activated Cdc42-Associated Kinase 1 (ACK1/TNK2) for the Treatment of Cancers,Journal of Medicinal Chemistry

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Small Molecules Targeting Activated Cdc42-Associated Kinase 1 (ACK1/TNK2) for the Treatment of Cancers
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2021-11-04 , DOI: 10.1021/acs.jmedchem.1c01030
Aoxue Wang ₁ , Junping Pei ₁ , Wen Shuai ₁ , Congcong Lin ₁ , Lu Feng ₁ , Yuxi Wang ₁ , Feng Lin _{1,

2} , Liang Ouyang ₁ , Guan Wang ₁

Affiliation

Activated Cdc42-associated kinase 1 (ACK1/TNK2) is a nonreceptor tyrosine kinase with a unique structure. It not only can act as an activated transmembrane effector of receptor tyrosine kinases (RTKs) to transmit various RTK signals but also can play a corresponding role in epigenetic regulation. A number of studies have shown that ACK1 is a carcinogenic factor. Blockage of ACK1 has been proven to be able to inhibit cancer cell survival, proliferation, migration, and radiation resistance. Thus, ACK1 is a promising potential antitumor target. To date, despite many efforts to develop ACK1 inhibitors, no specific small molecule inhibitors have entered clinical trials. This Perspective provides an overview of the structural features, biological functions, and association with diseases of ACK1 and in vitro and in vivo activities, selectivity, and therapeutic potential of small molecule ACK1 inhibitors with different chemotypes.

中文翻译：

靶向激活的 Cdc42 相关激酶 1 (ACK1/TNK2) 的小分子治疗癌症

活化的 Cdc42 相关激酶 1 (ACK1/TNK2) 是一种具有独特结构的非受体酪氨酸激酶。它不仅可以作为受体酪氨酸激酶（RTKs）的活化跨膜效应器传递各种RTK信号，而且可以在表观遗传调控中发挥相应的作用。多项研究表明，ACK1是一种致癌因子。已经证明 ACK1 的阻断能够抑制癌细胞的存活、增殖、迁移和辐射抗性。因此，ACK1 是一个很有前景的潜在抗肿瘤靶点。迄今为止，尽管在开发 ACK1 抑制剂方面付出了很多努力，但还没有特定的小分子抑制剂进入临床试验。该观点概述了 ACK1 的结构特征、生物学功能以及与疾病的关联以及体外和不同化学型的小分子 ACK1 抑制剂的体内活性、选择性和治疗潜力。

更新日期：2021-11-25

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