Advances in the development of phosphodiesterase-4 inhibitors

Gang Li; Dengqin He; Xiaojia Cai; Wen Guan; Yali Zhang; Jia-Qiang Wu; Hongliang Yao

doi:10.1016/j.ejmech.2023.115195

Advances in the development of phosphodiesterase-4 inhibitors

Eur J Med Chem. 2023 Mar 15:250:115195. doi: 10.1016/j.ejmech.2023.115195. Epub 2023 Feb 9.

Authors

Gang Li¹, Dengqin He², Xiaojia Cai², Wen Guan¹, Yali Zhang¹, Jia-Qiang Wu², Hongliang Yao³

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 School of Biotechnology and Health Sciences, Wuyi University, 22 Dongchengcun, Jianmen, 529020, China.
³ 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@giabr.gd.cn.

PMID: 36809706
DOI: 10.1016/j.ejmech.2023.115195

Abstract

Phosphodiesterase 4 (PDE4) hydrolyzes cyclic adenosine monophosphate (cAMP) and plays a vital roles in many biological processes. PDE4 inhibitors have been widely studied as therapeutics for the treatment of various diseases, including asthma, chronic obstructive pulmonary disease (COPD) and psoriasis. Many PDE4 inhibitors have progressed to clinical trials and some have been approved as therapeutic drugs. Although many PDE4 inhibitors have been approved to enter clinical trials, however, the development of PDE4 inhibitors for the treatment of COPD or psoriasis has been hampered by their side effects of emesis. Herein, this review summarizes advances in the development of PDE4 inhibitors over the last ten years, focusing on PDE4 sub-family selectivity, dual target drugs, and therapeutic potential. Hopefully, this review will contribute to the development of novel PDE4 inhibitors as potential drugs.

Keywords: Asthma; COPD; PDE4; Psoriasis; cAMP.

Publication types

Review

MeSH terms

Asthma* / drug therapy
Cyclic Nucleotide Phosphodiesterases, Type 4
Humans
Phosphodiesterase 4 Inhibitors* / pharmacology
Phosphodiesterase 4 Inhibitors* / therapeutic use
Psoriasis* / chemically induced
Pulmonary Disease, Chronic Obstructive* / drug therapy

Substances

Phosphodiesterase 4 Inhibitors
Cyclic Nucleotide Phosphodiesterases, Type 4