PDE7

The expression of phosphodiesterase 7A (PDE7A) and phosphodiesterase 8A (PDE8) genes is integral to human signaling pathways, and the inhibition of PDE7A has been associated with the onset of various diseases, including effects on the immune system and nervous system. The development of PDE7 selective inhibitors can promote research on immune and nervous system diseases, such as multiple sclerosis, chronic inflammation, and autoimmune responses. PDE8A is expressed alongside PDE8B, and its inhibitory mechanism is still unclear...

An unreported prenylated indole derivative hydroxytakakiamide ( 4 ) was isolated, together with the previously described ergosterol ( 1 ), ergosterol acetate ( 2 ), and (3 R )-3-(1 H -indol-3-ylmethyl)-3, 4-dihydro-1 H -1,4-benzodiazepine-2,5-dione ( 3 ), from the column fractions of the crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus fischeri MMERU 23. The structure of 4 was elucidated by the interpretation of 1D and 2D NMR spectral data and high-resolution mass spectrum...

The leaves, flowers, seeds, and bark of the Nyctanthes arbor-tristis Linn plant have been pharmacologically evaluated to signify the medicinal importance traditionally described for various ailments. We evaluated the anti-inflammatory potentials of 26 natural compounds using AutoDock 4.2 and Molecular Dynamics (MDS) performed with the GROMACS tool. SwissADME evaluated ADME (adsorption, distribution, metabolism, and excretion) parameters. Arb_E and Beta-sito, natural compounds of the plant, showed significant levels of binding affinity against COX-1, COX-2, PDE4, PDE7, IL-17A, IL-17D, TNF-α, IL-1β, prostaglandin E2, and prostaglandin F synthase...

Traumatic spinal cord injury (SCI) is characterized by severe neuroinflammation and hampered neuroregeneration, which often leads to permanent neurological deficits. Current therapies include decompression surgery, rehabilitation, and in some instances, the use of corticosteroids. However, the golden standard of corticosteroids still achieves minimal improvements in functional outcomes. Therefore, new strategies tackling the initial inflammatory reactions and stimulating endogenous repair in later stages are crucial to achieving functional repair in SCI patients...

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that hydrolyse the intracellular second messengers cAMP and cGMP to their inactive forms 5'AMP and 5'GMP. Some members of the PDE family display specificity towards a single cyclic nucleotide messenger, and PDE4, PDE7, and PDE8 specifically hydrolyse cAMP. While the role of PDE4 and its use as a therapeutic target have been well studied, less is known about PDE7 and PDE8. This review aims to collate the present knowledge on human PDE7 and outline its potential use as a therapeutic target...

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among non-contagious diseases in the world. PDE inhibitors are among current medicines prescribed for COPD treatment of which, PDE-4 family is the predominant PDE isoform involved in hydrolyzing cyclic adenosine monophosphate (cAMP) that regulates the inflammatory responses in neutrophils, lymphocytes, macrophages and epithelial cells The aim of this study is to investigate the cellular and molecular mechanisms of cAMP-PDE signaling, as an important pathway in the treatment management of patients with COPD...

Phosphodiesterase 7 (PDE7) specifically hydrolyzes cyclic adenosine monophosphate (cAMP), a second messenger that plays essential roles in cell signaling and physiological processes. Many PDE7 inhibitors used to investigate the role of PDE7 have displayed efficacy in the treatment of a wide range of diseases, such as asthma and central nervous system (CNS) disorders. Although PDE7 inhibitors are developed more slowly than PDE4 inhibitors, there is increasing recognition of PDE7 inhibitors as potential therapeutics for no nausea and vomiting secondary...

Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune and degenerative disease with axonal damage and demyelination as its main features. Its dual neurological and autoimmune nature makes it a disease that is difficult to treat. Treatments that simultaneously stop the immune response while protecting and repairing the nervous system are urgent. That is of utmost importance for the primary progressive multiple sclerosis (PPMS), a rare and severe variant of MS, characterized by worsening neurological function from the onset of symptoms...

Neurodegenerative illness develops as a result of genetic defects that cause changes at numerous levels, including genomic products and biological processes. It entails the degradation of cyclic nucleotides, cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP). PDE7 modulates intracellular cAMP signalling, which is involved in numerous essential physiological and pathological processes. For the therapy of neurodegenerative illnesses, the normalization of cyclic nucleotide signalling through PDE inhibition remains intriguing...

BACKGROUND: PDEs regulate cAMP levels which is critical for PKA activity-dependent activation of CREB-mediated transcription in learning and memory. Inhibitors of PDEs like PDE4 and Pde7 improve learning and memory in rodents. However, the role of PDE7 in cognition or learning and memory has not been reported yet. METHODS: Therefore, we aimed to explore the cognitive effects of a PDE7 subtype, PDE7a, using combined pharmacological and genetic approaches. RESULTS: PDE7a-nko mice showed deficient working memory, impaired novel object recognition, deficient spatial learning & memory, and contextual fear memory, contrary to enhanced cued fear memory, highlighting the potential opposite role of PDE7a in the hippocampal neurons...

Current treatment strategies of autoimmune diseases (ADs) display a limited efficacy and cause numerous adverse effects. Phosphodiesterase (PDE)4 and PDE7 inhibitors have been studied recently as a potential treatment of a variety of ADs. In this study, a PK/PD disease progression modeling approach was employed to evaluate effects of a new theophylline derivative, compound 34 , being a strong PDE4 and PDE7 inhibitor. Activity of the studied compound against PDE1 and PDE3 in vitro was investigated. Animal models of multiple sclerosis (MS), rheumatoid arthritis (RA), and autoimmune hepatitis were utilized to assess the efficacy of this compound, and its pharmacokinetics was investigated in mice and rats...

Asian sand dust (ASD), which mainly originates in China and Mongolia in the spring and blows into Korea, can exacerbate respiratory and immunological diseases. This study aims to observe effects of co-exposure to ASD on ovalbumin (OVA)-induced asthmatic lung inflammation and of treatment with a phosphodiesterase 7 (PDE7) inhibitor in a mouse model. The challenge with OVA increased airway hyperresponsiveness (AHR) and inflammatory cell infiltration into the lung tissue. Interleukin (IL)-13, tumor necrosis factor-alpha, monocyte-protein-1, mucin, and antigen-specific IgE and IgG1 production increased in mouse serum...

Phosphodiesterase (PDE) inhibitors are currently an extensively studied group of compounds that can bring many benefits in the treatment of various inflammatory and fibrotic diseases, including asthma. Herein, we describe a series of novel N'-phenyl- or N'-benzylbutanamide and N'-arylidenebutanehydrazide derivatives of 8-aminopurine-2,6-dione (27-43) and characterized them as prominent pan-PDE inhibitors. Most of the compounds exhibited antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)-induced murine macrophages RAW264...

Phosphodiesterase 7 (PDE7), one of the 11 phosphodiesterase (PDE) families, specifically hydrolyzes cyclic 3', 5'-adenosine monophosphate (cAMP). PDE7 is involved in many important functional processes in physiology and pathology by regulating intracellular cAMP signaling. Studies have demonstrated that PDE7 is widely expressed in the central nervous system (CNS) and potentially related to pathogenesis of many CNS diseases. Here, we summarized the classification and distribution of PDE7 in the brain and its functional roles in the mediation of CNS diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and schizophrenia...

Ischemic stroke is caused by a thromboembolic occlusion of a major cerebral artery, with the impaired blood flow triggering neuroinflammation and subsequent neuronal damage. Both the innate immune system (e.g., neutrophils, monocytes/macrophages) in the acute ischemic stroke phase and the adaptive immune system (e.g., T cells, B cells) in the chronic phase contribute to this neuroinflammatory process. Considering that the available therapeutic strategies are insufficiently successful, there is an urgent need for novel treatment options...

Background : About 5 million people die from diseases related to nicotine addiction and tobacco use each year. Nicotine-induced increase of corticomesolimbic dopaminergic (DAergic) transmission and hypodopaminergic conditions occurring during abstinence are important for maintaining drug-use habits. Methods : We examined the notion of re-equilibrating DAergic transmission by inhibiting phosphodiesterase 7 (PDE7), an intracellular enzyme highly expressed in the corticomesolimbic circuitry and responsible for the degradation of cyclic adenosine monophosphate (cAMP), the main second messenger modulated by DA receptor activation...

This study aimed to assess the efficacy and explore the mechanisms of action of a potent phosphodiesterase (PDE)7A and a moderate PDE4B inhibitor GRMS-55 in a mouse model of autoimmune hepatitis (AIH). The concentrations of GRMS-55 and relevant biomarkers were measured in the serum of BALB/c mice with concanavalin A (ConA)-induced hepatitis administered with GRMS-55 at two dose levels. A semi-mechanistic PK/PD/disease progression model describing the time courses of measured biomarkers was developed. The emetogenicity as a potential side effect of the studied compound was evaluated in the α2 -adrenoceptor agonist-induced anesthesia model...

Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7's role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-( 1H )-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies...

Introduction: Phosphodiesterases (PDEs) are isoenzymes ubiquitously expressed in the lungs where they catalyse cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (GMP), which are fundamental second messengers in asthma, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signaling pathways and, consequently, myriad biological responses. The superfamily of PDEs is composed of 11 families with a distinct substrate specificity, molecular structure and subcellular localization...

PURPOSE: Phosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11 C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7. METHODS: [11 C]MTP38 was radiosynthesized by 11 C-cyanation of a bromo precursor with [11 C]HCN. PET scans of rat and rhesus monkey brains and in vitro autoradiography of brain sections derived from these species were conducted with [11 C]MTP38...