TY - JOUR
T1 - An Overview of PDE4 Inhibitors in Clinical Trials
T2 - 2010 to Early 2022
AU - Crocetti, Letizia
AU - Floresta, Giuseppe
AU - Cilibrizzi, Agostino
AU - Giovannoni, Maria Paola
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - clinical trials
KW - COVID-19
KW - neurological disorders
KW - PDE4 inhibitors
KW - phosphodiesterase 4
KW - respiratory diseases
KW - rheumatoid arthritis
KW - skin diseases
UR - http://www.scopus.com/inward/record.url?scp=85136341858&partnerID=8YFLogxK
U2 - 10.3390/molecules27154964
DO - 10.3390/molecules27154964
M3 - Review article
C2 - 35956914
AN - SCOPUS:85136341858
SN - 1420-3049
VL - 27
JO - Molecules (Basel, Switzerland)
JF - Molecules (Basel, Switzerland)
IS - 15
M1 - 4964
ER -