Therapeutic potential of the sphingosine kinase 1 inhibitor, PF-543

Xueliang Yi; Xuemei Tang; Tianlong Li; Lin Chen; Hongli He; Xiaoxiao Wu; Chunlin Xiang; Min Cao; Zixiang Wang; Yi Wang; Yiping Wang; Xiaobo Huang

doi:10.1016/j.biopha.2023.114401

Therapeutic potential of the sphingosine kinase 1 inhibitor, PF-543

Biomed Pharmacother. 2023 Jul:163:114401. doi: 10.1016/j.biopha.2023.114401. Epub 2023 May 9.

Authors

Xueliang Yi¹, Xuemei Tang², Tianlong Li², Lin Chen³, Hongli He¹, Xiaoxiao Wu², Chunlin Xiang², Min Cao⁴, Zixiang Wang³, Yi Wang⁵, Yiping Wang⁶, Xiaobo Huang⁷

Affiliations

¹ Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; University of Electronic Science and Technology of China, China.
² Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
³ University of Electronic Science and Technology of China, China.
⁴ Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
⁵ Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; University of Electronic Science and Technology of China, China. Electronic address: w_yi2022@163.com.
⁶ Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; University of Electronic Science and Technology of China, China. Electronic address: wangyiping@uestc.edu.cn.
⁷ Department of ICU, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; University of Electronic Science and Technology of China, China. Electronic address: drhuangxb@163.com.

PMID: 37167721
DOI: 10.1016/j.biopha.2023.114401

Abstract

PF-543 is a sphingosine kinase 1（SPHK1）inhibitor developed by Pfizer and is currently considered the most potent selective SPHK1 inhibitor. SPHK1 catalyses the production of sphingosine 1-phosphate (S1P) from sphingosine. It is the rate-limiting enzyme of S1P production, and there is substantial evidence to support a very important role for sphingosine kinase in health and disease. This review is the first to summarize the role and mechanisms of PF-543 as an SPHK1 inhibitor in anticancer, antifibrotic, and anti-inflammatory processes, providing new therapeutic leads and ideas for future research and clinical trials.

Keywords: Anti-inflammatory; Anticancer; Antifibrotic; PF-543; S1P; SPHK1.

Publication types

Review

MeSH terms

Phosphotransferases (Alcohol Group Acceptor)*
Sphingosine*

Substances

sphingosine kinase
PF-543
sphingosine 1-phosphate
Sphingosine
Phosphotransferases (Alcohol Group Acceptor)