An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022

Molecules. 2022 Aug 4;27(15):4964. doi: 10.3390/molecules27154964.


Since the early 1980s, phosphodiesterase 4 (PDE4) has been an attractive target for the treatment of inflammation-based diseases. Several scientific advancements, by both academia and pharmaceutical companies, have enabled the identification of many synthetic ligands for this target, along with the acquisition of precise information on biological requirements and linked therapeutic opportunities. The transition from pre-clinical to clinical phase was not easy for the majority of these compounds, mainly due to their significant side effects, and it took almost thirty years for a PDE4 inhibitor to become a drug i.e., Roflumilast, used in the clinics for the treatment of chronic obstructive pulmonary disease. Since then, three additional compounds have reached the market a few years later: Crisaborole for atopic dermatitis, Apremilast for psoriatic arthritis and Ibudilast for Krabbe disease. The aim of this review is to provide an overview of the compounds that have reached clinical trials in the last ten years, with a focus on those most recently developed for respiratory, skin and neurological disorders.

Keywords: COVID-19; PDE4 inhibitors; clinical trials; neurological disorders; phosphodiesterase 4; respiratory diseases; rheumatoid arthritis; skin diseases.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic*
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Dermatitis, Atopic / drug therapy
  • Humans
  • Phosphodiesterase 4 Inhibitors* / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy


  • Phosphodiesterase 4 Inhibitors
  • Cyclic Nucleotide Phosphodiesterases, Type 4

Grant support

This research received no external funding.