Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents

Yang Li; Qing Lu; Chenghu Xie; Yiming Yu; Ao Zhang

doi:10.3389/fphar.2022.956220

Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents

Front Pharmacol. 2022 Aug 29:13:956220. doi: 10.3389/fphar.2022.956220. eCollection 2022.

Authors

Yang Li¹, Qing Lu¹, Chenghu Xie¹, Yiming Yu¹, Ao Zhang^{1

2}

Affiliations

¹ Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
² School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

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.

Keywords: clinical progress; immune infiltration; oncotherapy; p21-activated kinase 4; small molecular inhibitors.

Publication types

Review