Research progress on phosphatidylinositol 4-kinase inhibitors

Gang Li; Yanting Wu; Yali Zhang; Huamin Wang; Mengjie Li; Dengqin He; Wen Guan; Hongliang Yao

doi:10.1016/j.bcp.2023.115993

Research progress on phosphatidylinositol 4-kinase inhibitors

Biochem Pharmacol. 2024 Feb:220:115993. doi: 10.1016/j.bcp.2023.115993. Epub 2023 Dec 25.

Authors

Gang Li¹, Yanting Wu², Yali Zhang¹, Huamin Wang¹, Mengjie Li¹, Dengqin He³, Wen Guan¹, Hongliang Yao⁴

Affiliations

¹ Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China.
² Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; Department of Chemistry, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, 999077, China.
³ School of Biotechnology and Health Science, Wuyi University, 22 Dongchengcun, Jiangmen, Guangdong, 529020, China.
⁴ Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China. Electronic address: yaohl@giz.gd.cn.

PMID: 38151075
DOI: 10.1016/j.bcp.2023.115993

Abstract

Phosphatidylinositol 4-kinases (PI4Ks) could phosphorylate phosphatidylinositol (PI) to produce phosphatidylinositol 4-phosphate (PI4P) and maintain its metabolic balance and location. PI4P, the most abundant monophosphate inositol in eukaryotic cells, is a precursor of higher phosphoinositols and an essential substrate for the PLC/PKC and PI3K/Akt signaling pathways. PI4Ks regulate vesicle transport, signal transduction, cytokinesis, and cell unity, and are involved in various physiological and pathological processes, including infection and growth of parasites such as Plasmodium and Cryptosporidium, replication and survival of RNA viruses, and the development of tumors and nervous system diseases. The development of novel drugs targeting PI4Ks and PI4P has been the focus of the research and clinical application of drugs, especially in recent years. In particular, PI4K inhibitors have made great progress in the treatment of malaria and cryptosporidiosis. We describe the biological characteristics of PI4Ks; summarize the physiological functions and effector proteins of PI4P; and analyze the structural basis of selective PI4K inhibitors for the treatment of human diseases in this review. Herein, this review mainly summarizes the developments in the structure and enzyme activity of PI4K inhibitors.

Keywords: Alzheimer; Malaria; Nervous system disease; PI4K; PI4P; Tumor.

Publication types

Review

MeSH terms

1-Phosphatidylinositol 4-Kinase
Cryptosporidiosis*
Cryptosporidium* / metabolism
Humans
Phosphatidylinositol 3-Kinases / metabolism
Phosphatidylinositol Phosphates
Phosphatidylinositols / metabolism

Substances

1-Phosphatidylinositol 4-Kinase
Phosphatidylinositol 3-Kinases
Phosphatidylinositol Phosphates
Phosphatidylinositols