Research progress of phosphatidylinositol 4-kinase and its inhibitors in inflammatory diseases

Yan-Ping Li; Reyaj Mikrani; Yi-Fan Hu; Mirza Muhammad Faran Ashraf Baig; Muhammad Abbas; Fahad Akhtar; Ming Xu

doi:10.1016/j.ejphar.2021.174300

Research progress of phosphatidylinositol 4-kinase and its inhibitors in inflammatory diseases

Eur J Pharmacol. 2021 Sep 15:907:174300. doi: 10.1016/j.ejphar.2021.174300. Epub 2021 Jul 1.

Authors

Yan-Ping Li¹, Reyaj Mikrani², Yi-Fan Hu¹, Mirza Muhammad Faran Ashraf Baig³, Muhammad Abbas⁴, Fahad Akhtar⁵, Ming Xu⁶

Affiliations

¹ Department of Clinical Pharmacy, School of Preclinical Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
² Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria 3052, Australia.
³ Laboratory of Biomedical Engineering for Novel Bio-functional and Pharmaceutical Nano-materials, Prince Philip Dental Hospital, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, 999077, China.
⁴ State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, PR China.
⁵ State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China; School of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
⁶ Department of Clinical Pharmacy, School of Preclinical Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: mingxu@cpu.edu.cn.

PMID: 34217706
DOI: 10.1016/j.ejphar.2021.174300

Abstract

Phosphatidylinositol 4-kinase (PI4K) is a lipid kinase that can catalyze the transfer of phosphate group from ATP to the inositol ring of phosphatidylinositol (PtdIns) resulting in the phosphorylation of PtdIns at 4-OH sites, to generate phosphatidylinositol 4-phosphate (PI4P). Studies on biological functions reveal that PI4K is closely related to the occurrence and development of various inflammatory diseases such as obesity, cancer, viral infections, malaria, Alzheimer's disease, etc. PI4K-related inhibitors have been found to have the effects of inhibiting virus replication, anti-cancer, treating malaria and reducing rejection in organ transplants, among which MMV390048, an anti-malaria drug, has entered phase II clinical trial. This review discusses the classification, structure, distribution and related inhibitors of PI4K and their role in the progression of cancer, viral replication, and other inflammation induced diseases to explore their potential as therapeutic targets.

Keywords: Cancer; Inflammation; PI4K inhibitors; Phosphatidylinositol 4-kinase; Virus replication.

Publication types

Review

MeSH terms

1-Phosphatidylinositol 4-Kinase*
Phosphorylation
Virus Replication

Substances

1-Phosphatidylinositol 4-Kinase