{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T13:06:35Z","timestamp":1793451995602,"version":"4.5.0"},"reference-count":176,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/molecules27154964","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T02:12:39Z","timestamp":1659665559000},"page":"4964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3473-2683","authenticated-orcid":false,"given":"Letizia","family":"Crocetti","sequence":"first","affiliation":[{"name":"NEUROFARBA, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-1260","authenticated-orcid":false,"given":"Giuseppe","family":"Floresta","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9711-5183","authenticated-orcid":false,"given":"Agostino","family":"Cilibrizzi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Science, King\u2019s College London, Stamford Street, London SE1 9NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Giovannoni","sequence":"additional","affiliation":[{"name":"NEUROFARBA, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0021-9258(19)77423-7","article-title":"Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles","volume":"232","author":"Sutherland","year":"1958","journal-title":"J. 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