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

Phosphodiesterase‑4 inhibitors: a review of current developments (2013–2021)

(2022) Zhihao Liu et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Novel Liposomal Rolipram Formulation for Clinical Application to Reduce Emesis

(2022) Leila Gobejishvili et al.   Drug Design Development and Therapy

PDE4 inhibition as a therapeutic strategy for improvement of pulmonary dysfunctions in Covid-19 and cigarette smoking

(2021) Claire Lugnier et al.   BIOCHEMICAL PHARMACOLOGY

Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial

(2021) Elizabeth M. Berry-Kravis et al.   NATURE MEDICINE

Update on the Pathogenesis and Therapy of Atopic Dermatitis

(2021) Huaguo Li et al.   CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY

Rolipram rescues memory consolidation deficits caused by sleep deprivation: Implication of the cAMP/PKA and cAMP/Epac pathways

(2021) Ahmed Maher et al.   CNS & Neurological Disorders-Drug Targets

The Molecular Biology of Phosphodiesterase 4 Enzymes as Pharmacological Targets: An Interplay of Isoforms, Conformational States, and Inhibitors

(2021) Dean Paes et al.   PHARMACOLOGICAL REVIEWS

The Therapeutic Landscape of Rheumatoid Arthritis: Current State and Future Directions

(2021) Shahin Shams et al.   Frontiers in Pharmacology

The Immune Response in Multiple Sclerosis

(2021) Sofía Rodríguez Murúa et al.   Annual Review of Pathology-Mechanisms of Disease

Effects of chronic inhibition of phosphodiesterase-4D on behavior and regional rates of cerebral protein synthesis in a mouse model of fragile X syndrome

(2021) Michael Rosenheck et al.   NEUROBIOLOGY OF DISEASE

Pathophysiology, Clinical Presentation, and Treatment of Psoriasis

(2020) April W. Armstrong et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Advances in the development of phosphodiesterase-4 inhibitors

(2020) Ting Peng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhaled Phosphodiesterase 4 (PDE4) Inhibitors for Inflammatory Respiratory Diseases

(2020) Jonathan E. Phillips   Frontiers in Pharmacology

Role of phosphodiesterase-4 inhibitors in chronic obstructive pulmonary disease

(2020) Chin Kook Rhee et al.   KOREAN JOURNAL OF INTERNAL MEDICINE

Systemic Lupus Erythematosus

(2020) Marianthi Kiriakidou et al.   ANNALS OF INTERNAL MEDICINE

Phosphodiesterase Inhibitors: Could They Be Beneficial for the Treatment of COVID-19?

(2020) Mauro Giorgi et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Phosphodiesterase-4 enzyme as a therapeutic target in neurological disorders

(2020) Abid Bhat et al.   PHARMACOLOGICAL RESEARCH

NCS 613, a PDE4 inhibitor, by increasing cAMP level suppresses systemic inflammation and immune complexes deposition in kidney of MRL/lpr lupus- prone mice

(2020) Issaka Yougbare et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Phosphodiesterase 5 (PDE5): Structure-function regulation and therapeutic applications of inhibitors

(2020) Wesam S. Ahmed et al.   BIOMEDICINE & PHARMACOTHERAPY

Diagnosis and Outpatient Management of Chronic Obstructive Pulmonary Disease

(2019) Craig M. Riley et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders

(2019) Mark E. Gurney et al.   JOURNAL OF MEDICINAL CHEMISTRY

Management strategies and future directions for systemic lupus erythematosus in adults

(2019) Laura Durcan et al.   LANCET

Targeting Phosphodiesterases—Towards a Tailor-Made Approach in Multiple Sclerosis Treatment

(2019) Melissa Schepers et al.   Frontiers in Immunology

“Apremilast and Psoriasis in the Real World: A Retrospective Case Series”

(2019) L. Dozier et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Inhibitors of phosphodiesterase as cancer therapeutics

(2018) Ting Peng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Phosphodiesterase 4 inhibitors

(2018) Rema Zebda et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Inhibitors of phosphodiesterases in the treatment of cough

(2018) Juraj Mokry et al.   RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY

Efficacy and safety of phosphodiesterase 4 inhibitors in patients with asthma: A systematic review and meta-analysis

(2018) Jian Luo et al.   RESPIROLOGY

Determination of a PDE4 inhibitor Hemay005 in human plasma and urine by UPLC–MS/MS and its application to a PK study

(2018) Xuemei Liu et al.   Bioanalysis

Atopic dermatitis

(2018) Stephan Weidinger et al.   Nature Reviews Disease Primers

The short term bronchodilator effects of the dual PDE3 and PDE4 inhibitor RPL554 in COPD

(2018) Dave Singh et al.   EUROPEAN RESPIRATORY JOURNAL

Comparative Effectiveness and Safety Between Milrinone or Dobutamine as Initial Inotrope Therapy in Cardiogenic Shock

(2018) Tyler C. Lewis et al.   JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS

Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis

(2018) Robert J. Fox et al.   NEW ENGLAND JOURNAL OF MEDICINE

Multiple sclerosis - a review

(2018) R. Dobson et al.   EUROPEAN JOURNAL OF NEUROLOGY

Diagnosis and Management of Rheumatoid Arthritis

(2018) Daniel Aletaha et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Diagnosis and Management of Atopic Dermatitis

(2018) Khalad Maliyar et al.   Advances in Skin & Wound Care

Ibudilast inhibits chemokine expression in rheumatoid synovial fibroblasts and exhibits immunomodulatory activity in experimental arthritis

(2018) Felix I.L. Clanchy et al.   Arthritis & Rheumatology

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases

(2018) Heng Li et al.   Frontiers in Pharmacology

Safety, tolerability, and pharmacokinetics of single and repeat ascending doses of CHF6001, a novel inhaled phosphodiesterase-4 inhibitor: two randomized trials in healthy volunteers

(2018) Fabrizia Mariotti et al.   International Journal of Chronic Obstructive Pulmonary Disease

Topical E6005/RVT-501, a novel phosphodiesterase 4 inhibitor, for the treatment of atopic dermatitis

(2017) Masutaka Furue et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

2% Crisaborole topical ointment for the treatment of mild-to-moderate atopic dermatitis

(2017) Alice C. Cheape et al.   Expert Review of Clinical Immunology

2-Year animal carcinogenicity results for crisaborole, a novel phosphodiesterase 4 inhibitor for atopic dermatitis

(2017) Vic Ciaravino et al.   JOURNAL OF DERMATOLOGICAL SCIENCE

Discovery and Optimization of Thiazolidinyl and Pyrrolidinyl Derivatives as Inhaled PDE4 Inhibitors for Respiratory Diseases

(2017) Laura Carzaniga et al.   JOURNAL OF MEDICINAL CHEMISTRY

Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease

(2017) Yumin Zhou et al.   NEW ENGLAND JOURNAL OF MEDICINE

Care management in amyotrophic lateral sclerosis

(2017) M.-H. Soriani et al.   REVUE NEUROLOGIQUE

Artrite reumatoide do idoso e do jovem

(2017) Ariane Carla Horiuchi et al.   Revista Brasileira De Reumatologia

Amyotrophic lateral sclerosis

(2017) Orla Hardiman et al.   Nature Reviews Disease Primers

Oral Phosphodiesterase-4 Inhibitors for Chronic Obstructive Pulmonary Disease “Super Exacerbators”

(2016) Jadwiga A. Wedzicha   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

In vivo effective dibenzo[ b , d ]furan-1-yl-thiazoles as novel PDE-4 inhibitors

(2016) Gopalan Balasubramanian et al.   BIOORGANIC & MEDICINAL CHEMISTRY

A new therapeutic for the treatment of moderate-to-severe plaque psoriasis: apremilast

(2016) Andrea Chiricozzi et al.   Expert Review of Clinical Immunology

PDE4B as a microglia target to reduce neuroinflammation

(2016) Damien D. Pearse et al.   GLIA

Crisaborole and its potential role in treating atopic dermatitis: overview of early clinical studies

(2016) LT Zane et al.   Immunotherapy

Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study

(2016) Fuminori Ohba et al.   JOURNAL OF DERMATOLOGICAL TREATMENT

OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study

(2016) Jon M. Hanifin et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Advances in the treatment of cutaneous lupus erythematosus

(2016) A Kuhn et al.   LUPUS

Phosphodiesterase-4 inhibition as a therapeutic strategy for metabolic disorders

(2016) C. Wu et al.   Obesity Reviews

A novel inhaled phosphodiesterase 4 inhibitor (CHF6001) reduces the allergen challenge response in asthmatic patients

(2016) D. Singh et al.   PULMONARY PHARMACOLOGY & THERAPEUTICS

Second Messengers

(2016) Alexandra C. Newton et al.   Cold Spring Harbor Perspectives in Biology

Roflumilast: a review of its use in the treatment of COPD

(2016) Jadwiga Wedzicha et al.   International Journal of Chronic Obstructive Pulmonary Disease

The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases

(2016) Verena Katharina Raker et al.   Frontiers in Immunology

Psoriasis

(2016) Jacqueline E. Greb et al.   Nature Reviews Disease Primers

A Brief Review of Chronic Obstructive Pulmonary Disease

(2016) James C Hogg   Canadian Respiratory Journal

Methotrexate as combination partner of TNF inhibitors and tocilizumab. What is reasonable from an immunological viewpoint?

(2015) Torsten Witte   CLINICAL RHEUMATOLOGY

Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats

(2015) Rishi Pal et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity

(2014) P.H. Schafer et al.   CELLULAR SIGNALLING

Discovery and Early Clinical Development of 2-{6-[2-(3,5-Dichloro-4-pyridyl)acetyl]-2,3-dimethoxyphenoxy}-N-propylacetamide (LEO 29102), a Soft-Drug Inhibitor of Phosphodiesterase 4 for Topical Treatment of Atopic Dermatitis

(2014) Jakob Felding et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel Class of Benzoic Acid Ester Derivatives as Potent PDE4 Inhibitors for Inhaled Administration in the Treatment of Respiratory Diseases

(2014) Elisabetta Armani et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Role of Cyclic Nucleotide Signaling Pathways in Cancer: Targets for Prevention and Treatment

(2014) Alexandra Fajardo et al.   Cancers

Phosphodiesterase 4-targeted treatments for autoimmune diseases

(2013) Neal Kumar et al.   BMC Medicine

NCS 613 exhibits anti-inflammatory effects on PBMCs from lupus patients by inhibiting p38 MAPK and NF-κB signalling pathways while reducing proinflammatory cytokine production

(2013) Issaka Yougbaré et al.   CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY

PDE4 as a target for cognition enhancement

(2013) Wito Richter et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

Characterization of the Cellular Activity of PDE 4 Inhibitors Using Two Novel PDE 4 Reporter Cell Lines

(2013) Frank Wunder et al.   MOLECULAR PHARMACEUTICS

Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD

(2013) Henrik Watz et al.   PULMONARY PHARMACOLOGY & THERAPEUTICS

Phosphodiesterases as Therapeutic Targets for Alzheimer's Disease

(2012) Ana García-Osta et al.   ACS Chemical Neuroscience

Disease Progression in MRL/lpr Lupus-Prone Mice Is Reduced by NCS 613, a Specific Cyclic Nucleotide Phosphodiesterase Type 4 (PDE4) Inhibitor

(2012) Thérèse Keravis et al.   PLoS One

NCS 613, a potent and specific PDE4 inhibitor, displays anti-inflammatory effects on human lung tissues

(2011) Issaka Yougbare et al.   AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

Phosphodiesterase 4 (PDE4) regulation of proinflammatory cytokine and chemokine release from rheumatoid synovial membrane

(2011) A. Crilly et al.   ANNALS OF THE RHEUMATIC DISEASES

Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments

(2011) Thérèse Keravis et al.   BRITISH JOURNAL OF PHARMACOLOGY

Anti-TNF Treatment in Rheumatoid Arthritis

(2011) Janina Geiler et al.   CURRENT PHARMACEUTICAL DESIGN

The phosphodiesterase-4 inhibitor rolipram reverses Aβ-induced cognitive impairment and neuroinflammatory and apoptotic responses in rats

(2011) Chuang Wang et al.   INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY

In Vivo Characterization of GSK256066, a High-Affinity Inhaled Phosphodiesterase 4 Inhibitor

(2011) A. T. Nials et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity

(2010) Pierfrancesco Biagini et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Anti-inflammatory activity of phosphodiesterase (PDE)-IV inhibitors in acute and chronic models of inflammation

(2010) L. SEKUT et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Phosphodiesterase 4 Inhibitors in Inflammatory Bowel Disease: A Comprehensive Review

(2010) Pooneh Salari-Sharif et al.   CURRENT PHARMACEUTICAL DESIGN

Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis

(2010) Fiona E McCann et al.   ARTHRITIS RESEARCH & THERAPY

Discovery of selective PDE4B inhibitors

(2009) Kenji Naganuma et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery and structure–activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis

(2009) Tsutomu Akama et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis

(2009) PH Schafer et al.   BRITISH JOURNAL OF PHARMACOLOGY

Ibudilast: a review of its pharmacology, efficacy and safety in respiratory and neurological disease

(2009) P Rolan et al.   EXPERT OPINION ON PHARMACOTHERAPY

Inhibition of cAMP Degradation Improves Regulatory T Cell-Mediated Suppression

(2009) T. Bopp et al.   JOURNAL OF IMMUNOLOGY

Discovery of (S)-N-{2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide (Apremilast), a Potent and Orally Active Phosphodiesterase 4 and Tumor Necrosis Factor-α Inhibitor

(2009) Hon-Wah Man et al.   JOURNAL OF MEDICINAL CHEMISTRY

Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to inhibit blood—brain barrier disruption in multiple sclerosis

(2009) Bibiana Bielekova et al.   Multiple Sclerosis Journal

Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety

(2009) Alex B Burgin et al.   NATURE BIOTECHNOLOGY

Enhanced PDE4B expression augments LPS-inducible TNF expression in ethanol-primed monocytes: relevance to alcoholic liver disease

(2008) Leila Gobejishvili et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Optimization and structure–activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: Identification of MK-0873, a potent and effective PDE4 inhibitor

(2008) Daniel Guay et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Phosphodiesterase 4 inhibitors in chronic obstructive pulmonary disease: a new approach to oral treatment

(2008) Graeme P. Currie et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

PDE4 inhibitors: current status

(2008) D Spina   BRITISH JOURNAL OF PHARMACOLOGY

NF-κB in inflammatory bowel disease

(2008) I. Atreya et al.   JOURNAL OF INTERNAL MEDICINE

MK-0873, a PDE4 inhibitor, does not influence the pharmacokinetics of theophylline in healthy male volunteers

(2008) J.D. Boot et al.   PULMONARY PHARMACOLOGY & THERAPEUTICS