- |||||||||| Journal: PDE4 modulates muscle signaling in cancer cachexia. (Pubmed Central) - Feb 8, 2026
found that tumor-derived signals suppress the cAMP-protein kinase A (PKA)-CREB1 axis, destabilizing mitochondrial homeostasis. Restoring cAMP signaling through phosphodiesterase 4 (PDE4) inhibition rescued mitochondrial function, highlighting a promising strategy to mitigate tumor-induced cachexia.
- |||||||||| Eucrisa (crisaborole) / Pfizer, roflumilast / Generic mfg., apremilast / Generic mfg.
Review, Journal: PDE4 Inhibitor-Responsive Dermatoses: An Emerging Concept in Dermatology. (Pubmed Central) - Feb 6, 2026
This suggests that PDE4 inhibitors may assume a similar complementary framework for treating "PDE4 inhibitor-responsive dermatoses." Certain formulations of PDE4 inhibitors (including apremilast, crisaborole, and roflumilast) have undergone rigorous investigation in clinical trials and demonstrated robust efficacy and safety in many dermatologic conditions, achieving United States Food and Drug Administration approval for atopic dermatitis, psoriasis, and seborrheic dermatitis. Herein, we summarize the clinical evidence supporting the emerging concept of "PDE4 inhibitor-responsive dermatoses" and propose that PDE4 inhibition offers an additional pathway to achieving desired clinical outcomes.
- |||||||||| lidocaine topical / Generic mfg., Proctofoam (pramoxine) / Viatris
Review, Journal: Basic Mechanisms of Itch and Advances in Clinical Management. (Pubmed Central) - Feb 4, 2026
New drugs targeting the mast cell such as BTK inhibitors, c-KIT inhibitors, and MRGPRX2 antagonists have robust anti-pruritic effects in mast cell-mediated diseases. Supportive measures, including psychosocial interventions, remain integral to long-term management.
- |||||||||| Journal: Roflupram Reduces 6-OHDA-Induced Cellular Damage in SH-SY5Y Cells by Inhibiting PDE4. (Pubmed Central) - Jan 29, 2026
Roflu has demonstrated a clear protective effect against cell damage caused by 6-OHDA, which is closely related to the inhibition of PDE4B. These findings indicate that Roflu has substantial preclinical potential as a therapeutic candidate for PD and other neurodegenerative disorders involving oxidative damage.
- |||||||||| Daliresp (roflumilast) / AstraZeneca, apremilast / Generic mfg.
Review, Journal: Trends in Inhibitors, Structural Modifications, and Structure-Function Relationships of Phosphodiesterase 4: A Review. (Pubmed Central) - Jan 28, 2026
Their lower toxicity, favorable biocompatibility, and structural diversity enable fine-tuning of potency and selectivity through rational modification. Integrating structural insights derived from crystallographic and computational studies with the optimization of natural compounds offers a sustainable and effective strategy for the development of safer, isoform-selective PDE4-targeted therapies.
- |||||||||| apremilast / Generic mfg.
Clinical, P3 data, Journal: Results from the 32-week, phase 3 DISCREET study of apremilast in patients with moderate to severe genital psoriasis. (Pubmed Central) - Jan 27, 2026
P3
Integrating structural insights derived from crystallographic and computational studies with the optimization of natural compounds offers a sustainable and effective strategy for the development of safer, isoform-selective PDE4-targeted therapies. Apremilast is an effective oral systemic therapy in patients with moderate to severe genital psoriasis and has shown consistent clinical efficacy, lessening of symptoms and quality-of-life benefit in DISCREET.
- |||||||||| Eucrisa (crisaborole) / Pfizer
Journal: Exploring the Therapeutic Potential of Crisaborole Gel in Atopic Dermatitis: A Review. (Pubmed Central) - Jan 27, 2026
Crisaborole's specific mechanism, safety profile, and effectiveness in interrupting the inflammatory cycle make it an attractive treatment alternative, according to this study. Crisaborole is presented here as a potential remedy to address the research gap: the need for safer, more efficient therapies that target inflammatory pathways in AD.
- |||||||||| Preclinical, Journal: Pharmacological characterization and preclinical evaluation of 11h: a novel, brain-penetrant PDE4 inhibitor for neurological disorders. (Pubmed Central) - Jan 26, 2026
Consistent with this experimental profile, molecular docking suggested that 11h preferentially engages a pocket within the PDE4 catalytic domain, with high predicted binding affinity and ligand efficiency driven by hydrophobic and electrostatic interactions. These findings suggest that 11h provides broad PDE4 inhibition with a favorable tolerability and pharmacokinetic profile relative to approved PDE4 inhibitors, supporting its further development as a therapeutic candidate for CNS disorders characterized by neuroinflammation.
- |||||||||| Eucrisa (crisaborole) / Pfizer
Journal: Topical Anti-Inflammatory Treatments for Atopic Dermatitis. (Pubmed Central) - Jan 21, 2026
Topical calcineurin inhibitors and crisaborole were associated with application-site irritation, and short-term topical steroid use was not associated with skin thinning. However, these findings were of low to moderate certainty, and longer-term data remain limited for many agents.
- |||||||||| Zyclara (imiquimod) / Mochida, Viatris, Bausch Health
Journal: Discovery of pinoresinol dimethyl ether as a natural PDE4 inhibitor with anti-psoriatic effects. (Pubmed Central) - Jan 19, 2026
In a murine imiquimod-induced psoriasis model, PDME treatment markedly alleviated psoriatic lesions, reduced skin thickening, and suppressed inflammatory responses. These findings highlight PDME as a promising natural PDE4 inhibitor with significant potential for the treatment of psoriasis.
- |||||||||| ivabradine / Generic mfg., propranolol / Generic mfg.
Preclinical, Journal: Contractile Effects of Glucagon in Mouse Cardiac Preparations. (Pubmed Central) - Jan 10, 2026
The fact that this study observed a decreases PDE4 expression and increases in AQP5 expression upon Rolipram administration might indicate a close relationship of these two parameters in inflammatory lung disease. The positive chronotropic effects of glucagon were also attenuated by 1
- |||||||||| apremilast / Generic mfg.
Journal: Susceptibility to Dermatophytosis in SDR9C7-Nonsyndromic Epidermal Differentiation Disorder: Observation of Cutaneous Inflammation Involving IRF4 and IL-17. (Pubmed Central) - Jan 9, 2026
Based on previous studies of decreased Irf4 mRNA in Sdr9c7-/- mice, IRF4 transcription factor-dependent IL-17 production, and the importance of IL-17A/F in mucocutaneous immunity against Candida albicans, we examined the expression of each molecule using immunofluorescence and found for the first time decreased IRF4 and IL17-A/C/F (which were further decreased by apremilast treatment) in SDR9C7-nEDD epidermis. Although further studies are needed to clarify an evaluation of cytokine profiles in SDR9C7-nEDD, which may have immune profiles different from the previously reported IL-17-dominant immune profiles in the major forms of ichthyosis, these findings might have contributed to susceptibility to dermatophytosis in this patient, and it is suggested that the use of apremilast should be avoided in SDR9C7-nEDD.
- |||||||||| Jascayd (nerandomilast) / Boehringer Ingelheim, nintedanib / Generic mfg., pirfenidone / Generic mfg.
Journal: Jascayd (nerandomilast): a novel PDE4B inhibitor for idiopathic pulmonary fibrosis. (Pubmed Central) - Jan 7, 2026
Long-term extension data demonstrate sustained safety and lung function preservation. Offering both monotherapy and combination potential, Jascayd establishes a new therapeutic class that targets inflammation and fibrosis concurrently, representing a pivotal advancement toward personalized, multi-pathway treatment in IPF.
- |||||||||| Preclinical, Journal: Selective inhibition of long isoforms of phosphodiesterase 4D mitigates liver fibrosis in mouse models. (Pubmed Central) - Jan 2, 2026
In a mouse model of liver fibrosis, genetic ablation of PDE4D or pharmacological inhibition using D159687, a selective allosteric inhibitor targeting the long isoforms of PDE4D, suppresses the expression of inflammatory and profibrogenic genes. These findings establish the long isoforms of PDE4D as key drivers of liver fibrosis and highlight their potential as therapeutic targets to ameliorate liver fibrosis.
- |||||||||| Journal: Cinobufagin Directly Targets PDE4D to Disrupt Fibroblast-Dendritic Cell Crosstalk in Atopic Dermatitis. (Pubmed Central) - Dec 29, 2025
Notably, PDE4D knockout mice exhibited diminished inflammation, mimicking the effects of cinobufagin and confirming a role for PDE4D in AD progression. These findings establish PDE4D as a critical driver of AD and demonstrate that cinobufagin effectively targets this pathway, offering a promising therapeutic approach for AD and related inflammatory skin disorders.
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron
Journal: Reaching for the Stars in Atopic Dermatitis: Efficacy, Safety, Tolerability, Accessibility, and Remission/Remittive Effects (ESTAR). (Pubmed Central) - Dec 25, 2025
By addressing critical factors such as efficacy (onset speed, depth, durability, and reliability), safety, tolerability, and remission potential, this framework can aid in evaluating emerging therapies with a patient-centered approach. The ESTAR framework emphasizes balancing immediate symptom relief with sustainable long-term disease control, offering tools such as a radar chart to help clinicians and patients navigate complex treatment options, improve adherence, and optimize outcomes in AD care.
- |||||||||| sildenafil / Generic mfg., Daliresp (roflumilast) / AstraZeneca, tadalafil / Generic mfg.
Review, Journal: Basic Science and Pathogenesis. (Pubmed Central) - Dec 24, 2025
Although present PDEIs benefit patients we need new studies that make these inhibitors more selective for specific isoforms and with fewer unwanted effects to create improved therapeutic drugs. Emerging technology in drug discovery including artificial intelligence and personalized treatment methods will guide the creation of better and safer PDE inhibitors to treat many diseases.
- |||||||||| chloroquine phosphate / Generic mfg., furosemide / Generic mfg.
Journal: Restoring autophagy flux by rolipram attenuates ototoxicity in Hearing loss. (Pubmed Central) - Dec 21, 2025
In this study we investigated whether enhancing autophagy can mitigate kanamycin and furosemide induced cytotoxicity by using rolipram to restore the autophagy flux...Consistent with an autophagy dependent mechanism, the protective effect of rolipram was abolished by chloroquine or Atg7 knockdown, confirming that intact autophagy flux is required for cellular protection...Notably, ribbon synapses of inner hair cells were also maintained, indicating that autophagy enhancement protected both cellular integrity and synaptic function. These findings demonstrate that restoring autophagy flux represents a viable therapeutic strategy against ototoxic injury, and identify rolipram as a potential pharmacological agent for protecting auditory cells and hearing function.
- |||||||||| apremilast / Generic mfg.
Clinical, Journal: Apremilast Versus Placebo for Genital Erosive Lichen Planus in Women: A Randomized Controlled Trial. (Pubmed Central) - Dec 19, 2025
These findings demonstrate that restoring autophagy flux represents a viable therapeutic strategy against ototoxic injury, and identify rolipram as a potential pharmacological agent for protecting auditory cells and hearing function. Although having a small sample size, this randomized controlled trial did not reveal any signals indicating a clinical effect from apremilast treatment in women with moderate-to-severe GELP.
- |||||||||| methotrexate / Generic mfg., azathioprine / Generic mfg.
Review, Journal: Updates from the AAD and AAAAI Guidelines for Managing Atopic Dermatitis. (Pubmed Central) - Dec 19, 2025
Key differences between the two recommendations include topical PDE-4 Inhibitors, topical JAK Inhibitors, systemic JAK inhibitors, azathioprine, methotrexate, and mycophenolate. The final difference between the AAD and JTF guidelines is that AAD categorizes evidence and comments on the certainty of association for each group of comorbidities, while JTF makes general statements regarding comorbidities.
- |||||||||| Journal: Phosphodiesterase-4 inhibition in localized scleroderma: A case series of topical roflumilast. (Pubmed Central) - Dec 19, 2025
Roflumilast, a potent phosphodiesterase-4 inhibitor with anti-inflammatory and antifibrotic properties, may offer a well-tolerated, nonimmunosuppressive treatment option in morphea. This is the first reported case series using topical roflumilast in localized scleroderma and supports further investigation of phosphodiesterase-4 inhibition as a therapeutic strategy in fibrosing skin disease.
- |||||||||| apremilast / Generic mfg.
Journal: Global Research Trends in Apremilast for Psoriasis: A Bibliometric Analysis (2008-2024). (Pubmed Central) - Dec 16, 2025
This bibliometric analysis demonstrates that research on Apremilast for psoriasis has evolved from clinical trials focused on efficacy and safety to broader applications in real-world settings, including nail psoriasis and pathogenesis. Future research is likely to concentrate on long-term outcomes, optimizing treatment regimens, and addressing unmet needs in psoriasis management, particularly among specific patient subgroups.
- |||||||||| Review, Journal: Pipeline treatments on psoriatic disease. (Pubmed Central) - Dec 12, 2025
While these innovations offer exciting opportunities for personalized medicine, challenges remain regarding long-term safety, optimal treatment sequencing, and combination strategies. Further randomized controlled trials and real-world data are necessary to define the most effective and sustainable treatment approaches for psoriatic disease.
- |||||||||| mufemilast (Hemay005) / Tianjin Hemay Pharma
Trial completion: Evaluation the Safety of hemay005 Tablets (clinicaltrials.gov) - Dec 9, 2025
P1, N=468, Completed,
The anti-inflammatory effects of ensifentrine were lower compared to the PDE4 inhibitors tested. Recruiting --> Completed
- |||||||||| Daliresp (roflumilast) / AstraZeneca
Journal: Successful treatment of lichen spinulosis with topical roflumilast: A case report. (Pubmed Central) - Dec 9, 2025
Topical roflumilast (0.3%) is a recently approved phosphodiesterase-4 inhibitor first used in psoriasis which has shown reduction in hyperkeratosis in vitro. We report on an adult with symptomatic and recalcitrant lichen spinulosis who achieved significant improvement with the use of topical roflumilast over a 6-month period.
|
