Cost-Effectiveness Study of Difamilast 1% for the Treatment of Atopic Dermatitis in Adult Japanese Patients DOI Creative Commons

Takeshi Nakahara,

Shinichi Noto,

Miyuki Matsukawa

и другие.

Dermatology and Therapy, Год журнала: 2024, Номер 14(11), С. 3113 - 3132

Опубликована: Ноя. 1, 2024

Difamilast has proven to be an effective treatment for the of atopic dermatitis (AD) in Japan, but its cost-effectiveness remains unknown. Therefore, objective current study was determine difamilast 1% compared with delgocitinib 0.5% Japanese adult patients moderate-to-severe AD and placebo all-severity from a public health-care perspective. The analysis conducted using model This had four health states ("clear," "mild," "moderate," "severe") defined according Eczema Area Severity Index score. time horizon 1 year. Because period short, no discount rate applied. proportions previously estimated by anchored matching-adjusted indirect comparison were implemented model. further populated data literature. main outcomes quality-adjusted life-years (QALY), costs, outcomes, including incremental ratio. All prices stated JPY at price level 2018 April 2019 March. One-way sensitivity probabilistic (PSA) performed assess robustness results. In base case, 827,054/QALY 1,518,657/QALY, respectively. PSA showed that 66.6% 99.6% probability being below 5 million/QALY threshold, results suggest is more cost-effective option

Язык: Английский

Signaling pathways and targeted therapies for psoriasis DOI Creative Commons
Jia Guo, H. Zhang,

Wenrui Lin

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 27, 2023

Abstract Psoriasis is a common, chronic, and inflammatory skin disease with high burden on individuals, health systems, society worldwide. With the immunological pathologies pathogenesis of psoriasis becoming gradually revealed, therapeutic approaches for this have gained revolutionary progress. Nevertheless, mechanisms less common forms remain elusive. Furthermore, severe adverse effects recurrence upon treatment cessation should be noted addressed during treatment, which, however, has been rarely explored integration preliminary findings. Therefore, it crucial to comprehensive understanding behind pathogenesis, which might offer new insights research lead more substantive progress in expand clinical options treatment. In review, we looked briefly introduce epidemiology, subtypes, pathophysiology, comorbidities systematically discuss signaling pathways involving extracellular cytokines intracellular transmission, as well cross-talk between them. discussion, also paid attention potential metabolic epigenetic molecular mechanistic cascades related its comorbidities. This review outlined current psoriasis, especially targeted therapies novel strategies, mechanism recurrence.

Язык: Английский

Процитировано

142

Novel Anti-Inflammatory Approaches to COPD DOI Creative Commons
Mario Cazzola, Nicola A. Hanania, Clive P. Page

и другие.

International Journal of COPD, Год журнала: 2023, Номер Volume 18, С. 1333 - 1352

Опубликована: Июнь 1, 2023

Airway inflammation, driven by different types of inflammatory cells and mediators, plays a fundamental role in COPD its progression. Neutrophils, eosinophils, macrophages, CD4

Язык: Английский

Процитировано

33

Design, Synthesis, and Evaluation of Selective PDE4 Inhibitors for the Therapy of Pulmonary Injury DOI
Mengjie Li, Gang Li, Liu Y

и другие.

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Pulmonary inflammation is the main cause of lung injury. Phosphodiesterase 4 (PDE4) a promising anti-inflammatory target for treatment respiratory diseases. Herein, we designed and synthesized 43 compounds in two novel series benzimidazole derivatives as PDE4 inhibitors. Among them, compound A5 showed highly selective inhibition PDE4, good safety, liver microsomal stability vitro. administration remarkably attenuated inflammatory infiltration pathologic injury models acute mice chronic obstructive pulmonary disease (COPD) mice. In addition, enhanced sputum secretion, relieved cough mice, inhibited phosphorylation p38 MAP kinase, an important protein regulation Overall, A5, effective inhibitor without toxicity gastrointestinal reaction, may be potent candidate

Язык: Английский

Процитировано

2

Beyond PDE4 inhibition: A comprehensive review on downstream cAMP signaling in the central nervous system DOI Open Access

Zoë Donders,

Iga Joanna Skorupska,

Emily Willems

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 117009 - 117009

Опубликована: Июнь 21, 2024

Cyclic adenosine monophosphate (cAMP) is a key second messenger that regulates signal transduction pathways pivotal for numerous biological functions. Intracellular cAMP levels are spatiotemporally regulated by their hydrolyzing enzymes called phosphodiesterases (PDEs). It has been shown increased in the central nervous system (CNS) promote neuroplasticity, neurotransmission, neuronal survival, and myelination while suppressing neuroinflammation. Thus, elevating through PDE inhibition provides therapeutic approach multiple CNS disorders, including sclerosis, stroke, spinal cord injury, amyotrophic lateral traumatic brain Alzheimer's disease. In particular, of cAMP-specific PDE4 subfamily widely studied because its high expression CNS. So far, clinical translation full inhibitors hampered dose-limiting side effects. Hence, focusing on signaling cascades downstream activated upon presents promising strategy, offering novel pharmacologically safe targets treating disorders. Yet, underlying PDE(4) remain partially elusive. This review comprehensive overview existing knowledge regarding mediators induced or stimulators. Furthermore, we highlight gaps future perspectives may incentivize additional research concerning inhibition, thereby providing approaches

Язык: Английский

Процитировано

8

PDE4D: A Multipurpose Pharmacological Target DOI Open Access
Matteo Lusardi, Federica Rapetti, Andrea Spallarossa

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8052 - 8052

Опубликована: Июль 24, 2024

Phosphodiesterase 4 (PDE4) enzymes catalyze cyclic adenosine monophosphate (cAMP) hydrolysis and are involved in a variety of physiological processes, including brain function, monocyte macrophage activation, neutrophil infiltration. Among different PDE4 isoforms, Phosphodiesterases 4D (PDE4Ds) play fundamental role cognitive, learning memory consolidation processes cancer development. Selective PDE4D inhibitors (PDE4Dis) could represent an innovative valid therapeutic strategy for the treatment various neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, Lou Gehrig’s but also stroke, traumatic spinal cord injury, mild cognitive impairment, all demyelinating diseases multiple sclerosis. In addition, small molecules able to block isoforms have been recently studied specific types, particularly hepatocellular carcinoma breast cancer. This review overviews PDE4DIsso far identified provides useful information, from medicinal chemistry point view, development novel series compounds with improved pharmacological properties.

Язык: Английский

Процитировано

8

Short PDE4 Isoforms as Drug Targets in Disease DOI Creative Commons
Elka Kyurkchieva, George S. Baillie

Frontiers in Bioscience-Landmark, Год журнала: 2023, Номер 28(7), С. 133 - 133

Опубликована: Июль 4, 2023

The second messenger, cyclic adenosine monophosphate (cAMP), is a master regulator of signal transduction that maintains cell homeostasis. A fine balance between cAMP synthesis by adenylyl cyclase and degradation phosphodiesterases (PDEs) underpins receptor-specific responses. As multiple receptors rely on for signaling, PDEs shape three-dimensional, localized gradients the nucleotide to drive appropriate signaling cascades. Of 11 PDE families, PDE4, which comprises long, short, supershort isoforms dead-short isoform, great interest due its implication in disease. Aberrant PDE4 expression post-translational modifications are hallmarks several clinical indications curative treatment not yet available. While some PDE4-specific small molecule inhibitors directed against active site approved use, they limited severe side effects owing high degree conservation catalytic domain over 20 unique isoforms. Some attempts use different modular structure exists long shorter now bearing success. However, these exclusively aimed at isoforms, have been focus majority research this area. Here, we summarised literature lesser-studied short provide record discovery, regulation, disease relevance class enzymes represent an untapped target specific inhibition future.

Язык: Английский

Процитировано

12

Hypersampsonone H attenuates ulcerative colitis via inhibition of PDE4 and regulation of cAMP/PKA/CREB signaling pathway DOI
Yanzhen Li, Mingqiang Wang,

Jianhui Su

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 128, С. 111490 - 111490

Опубликована: Янв. 13, 2024

Язык: Английский

Процитировано

4

Therapeutic Advances in Psoriasis: From Biologics to Emerging Oral Small Molecules DOI Creative Commons
Francesco Ferrara, Chiara Verduci,

Emanuela Laconi

и другие.

Antibodies, Год журнала: 2024, Номер 13(3), С. 76 - 76

Опубликована: Сен. 14, 2024

Psoriasis is a persistent, inflammatory condition affecting millions globally, marked by excessive keratinocyte proliferation, immune cell infiltration, and widespread inflammation. Over the years, therapeutic approaches have developed significantly, shifting from conventional topical treatments phototherapy to more sophisticated systemic interventions such as biologics and, recently, oral small-molecule drugs. This review seeks present comprehensive investigation of existing psoriasis treatment options, focusing on biologic agents, small molecules, emerging treatments. Several categories received regulatory approval for psoriasis, including TNF-α, IL-17, IL-12/23, IL-23 inhibitors. Biologics revolutionized psoriasis. These targeted therapies offer significant improvement in disease control quality life, with acceptable safety profiles. However, limitations cost, potential immunogenicity, administration challenges driven exploration alternative modalities. Oral particularly inhibitors Janus kinase (JAK), emerged options due their convenience efficacy. agents represent paradigm shift management condition, offering action specific signaling pathways. In addition therapies, explores that hold promise future care. include innovative Early-stage clinical trials suggest these may enhance outcomes patients. conclusion, landscape rapidly evolving, emphasizing targeted, patient-centered Ongoing research development are expected lead personalized effective strategies this complex condition.

Язык: Английский

Процитировано

3

Development of selective heterocyclic PDE4 inhibitors for treatment of psoriasis DOI

Gang Li,

Dengqin He,

Xudong Qian

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 280, С. 116930 - 116930

Опубликована: Окт. 9, 2024

Язык: Английский

Процитировано

3

Advances in the development of phosphodiesterase 5 inhibitors DOI

Tieqiang Zong,

Xing Huang,

Wei Zhou

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 287, С. 117365 - 117365

Опубликована: Фев. 6, 2025

Язык: Английский

Процитировано

0