2. Academic Validation
  3. Small Molecules Targeting Activated Cdc42-Associated Kinase 1 (ACK1/TNK2) for the Treatment of Cancers

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

  • J Med Chem. 2021 Nov 25;64(22):16328-16348. 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
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China.
  • 2 Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
PMID: 34735773 DOI: 10.1021/acs.jmedchem.1c01030
Abstract

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.

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