AUTHOR=Li Yang , Lu Qing , Xie Chenghu , Yu Yiming , Zhang Ao TITLE=Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.956220 DOI=10.3389/fphar.2022.956220 ISSN=1663-9812 ABSTRACT=

The p21-activated kinase 4 (PAK4) is a member of the PAKs family. It is overexpressed in multiple tumor tissues. Pharmacological inhibition of PAK4 attenuates proliferation, migration, and invasion of cancer cells. Recent studies revealed that inhibition of PAK4 sensitizes immunotherapy which has been extensively exploited as a new strategy to treat cancer. In the past few years, a large number of PAK4 inhibitors have been reported. Of note, the allosteric inhibitor KPT-9274 has been tested in phase Ⅰ clinic trials. Herein, we provide an update on recent research progress on the PAK4 mediated signaling pathway and highlight the development of the PAK4 small molecular inhibitors in recent 5 years. Meanwhile, challenges, limitations, and future developmental directions will be discussed as well.