Journal: Pharmaceutics

Article Title: Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology

doi: 10.3390/pharmaceutics17010091

Figure Lengend Snippet: Pro-inflammatory state: Lower levels of cAMP prevent the activation of PKA and Epac1/2, leading to increased NF-κB activity and the induction of pro-inflammatory mediators. Additionally, the activation of pCREB by PKA is reduced, leading to a decrease in the expression of anti-inflammatory mediators. Abbreviations: AC, Adenylate cyclase; PDE4, phosphodiesterase 4; PKA, protein kinase A; Epac1/2, exchange protein 1/2 activated by cAMP; pCREB, phosphorylated cAMP-responsive element binding protein; NF-kB, nuclear factor kappa-light chain-enhancer of activated B cells. Created with www.biorender.com (accessed on 9 January 2025).

Article Snippet: Hemay005 is an oral non-selective PDE4 inhibitor in development developed by Tianjin Hemay Pharmaceutical Co., Tianjin, China, for the treatment of psoriasis.

Techniques: Activation Assay, Activity Assay, Expressing, Binding Assay

Journal: Pharmaceutics

Article Title: Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology

doi: 10.3390/pharmaceutics17010091

Figure Lengend Snippet: PDE4 inhibitors’ mechanism of action: Upon inhibition of PDE4, intracellular levels of cAMP rise, leading to the activation of PKA and Epac1/2 and the subsequent inhibition of NF-kB. In addition, pCREB levels increase, promoting the production of anti-inflammatory mediators. Abbreviations: AC, Adenylate cyclase; PDE4, phosphodiesterase 4; PKA, protein kinase A; Epac1/2, exchange protein 1/2 activated by cAMP; pCREB, phosphorylated cAMP-responsive element binding protein; NF-kB, nuclear factor kappa-light chain-enhancer of activated B cells; iPDE4, inhibitor of PDE4. Created with www.biorender.com (accessed on 9 January 2025).

Article Snippet: Hemay005 is an oral non-selective PDE4 inhibitor in development developed by Tianjin Hemay Pharmaceutical Co., Tianjin, China, for the treatment of psoriasis.

Techniques: Inhibition, Activation Assay, Binding Assay

Journal: Pharmaceutics

Article Title: Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology

doi: 10.3390/pharmaceutics17010091

Figure Lengend Snippet: Overview of PDE4 inhibitors approved and under clinical development in dermatology.

Article Snippet: Hemay005 is an oral non-selective PDE4 inhibitor in development developed by Tianjin Hemay Pharmaceutical Co., Tianjin, China, for the treatment of psoriasis.

Techniques: Formulation

Journal: British Journal of Pharmacology

Article Title: The human G protein‐coupled ATP receptor P2Y 11 is a target for anti‐inflammatory strategies

doi: 10.1111/bph.15379

Figure Lengend Snippet: P2Y 11 receptor‐driven release of soluble TNF receptors depends on intracellular cAMP and on TACE/ADAM17: synergistic enhancement by IL‐1α and IL‐1ß (a) M2 macrophages were treated with ATPγS in the presence or absence of increasing concentrations of the phosphodiesterase (PDE) inhibitors IBMX (nonselective) or rolipram (PDE4‐selective). The antagonist NF340 was used to confirm that agonist‐mediated responses were specific to stimulation of P2Y 11 receptors. sTNFR2 was measured in cell culture supernatants. (b) M2 macrophages were treated with ATPγS in the presence or absence of increasing concentrations of the TACE/ADAM17 inhibitors TAPI‐1 and TAPI‐2. The antagonist NF340 was used to confirm that agonist‐mediated responses were specific to stimulation of P2Y 11 receptors. sTNFR2 was measured in cell culture supernatants. (c) M2 macrophages were treated for 24 h with increasing doses of IL‐1α or IL‐1ß either alone or in combination with the P2Y 11 receptor agonist ATPγS (10 μM). The antagonist NF340 (10 μM) was used to confirm that agonist‐mediated responses were specific to stimulation of P2Y 11 receptors. For all graphs, data shown are means ± SEM from five independent donors. * P ≤ .05, significantly different as indicated; one‐way ANOVA

Article Snippet: Additional reagents used in this study are as follows: P2X1 receptor antagonist NF449 (10 μM) (Tocris), adenylyl cyclase inhibitor SQ22536 (5 to 20 μM) (Tocris), Gq/11 inhibitor YM‐254890 (0.1 to 0.5 μM) (Adipogen Life Sciences, Liestal, Switzerland), recombinant IL‐1α and IL‐1ß (50 to 1,000 pg·ml −1 ) (R&D, Bio‐Techne), recombinant IL‐1 receptor antagonist (IRAP ; 0.05 to 0.2 μg·ml −1 ) (R&D, Bio‐techne); nonselective phosphodiesterase inhibitor 3‐isobutyl‐1‐methylxanthine (IBMX ) (20 to 200 μM) (Sigma‐Aldrich); PDE4‐ selective inhibitor rolipram (2 to 10 μM) (Sigma‐Aldrich), the TACE/ADAM17 inhibitors TAPI‐1 and TAPI‐2 (10 to 50 μM) (Tocris); lipopolysaccharide (LPS) from Salmonella abortus equi (10 pg·ml−1 to 10 ng·ml −1 ) (Sigma‐Aldrich) was used to activate M2 macrophages via TLR4.

Techniques: Cell Culture

Journal: Journal of Personalized Medicine

Article Title: Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis

doi: 10.3390/jpm11010020

Figure Lengend Snippet: The data obtained for 78 pre-selectedsingle-nucleotide polymorphisms(SNPs) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ] in patient groups with advanced and lowered target apremilast therapy clinical outcomes. SNP with statistically significant differences are labeled with a star *. The population was from European origin and were healthy. The“1000 Genomes” project is shown for reference.

Article Snippet: The monotherapy of the selective PDE4 inhibitor apremilast (Otezla ® , Celgene International Sarl, Boudry, Switzerland) was carried out for all patients according to the Russian Federal Clinical Recommendations on PV patient treatment.

Techniques: Labeling, Sequencing, Variant Assay

Journal: Neuron

Article Title: Precisely-timed nicotinic activation drives SST inhibition in neocortical circuits

doi: 10.1016/j.neuron.2018.01.037

Figure Lengend Snippet: KEY RESOURCES TABLE

Article Snippet: Pharmacology The following agents were used for bath-application in acute brain slice experiments: forskolin, cell-permeable activator of adenylyl cyclase (50 μM, Tocris), selective cAMP-specific phosphodiesterase (PDE4) inhibitor rolipram (0.1 μM, Sigma), the noradrenergic agonist norepinephrine (50 μM, Sigma), the serotonin receptor agonist serotonin (10 μM, Tocris), the dopamine receptor agonist CY 208–243 (50 μM, Tocris), P2 receptor agonist adenosine (100 μM, Sigma), the CB1 receptor antagonist AM 251 (1 μM, Tocris), the group I metabotropic glutamate receptor agonist DHPG (10 μM, Sigma).

Techniques: Plasmid Preparation, Recombinant, Software