Rat Pde4b (cAMP-specific 3',5'-cyclic phosphodiesterase 4B) ELISA Kit

The development of selective ligands binding to specific PDE isoforms represents an urgent need in medicinal chemistry, being a necessary strategy to identify many more drug-like compounds, to be investigated for several therapies. Concerning inflammation, rational design of selective PDE7 inhibitors over PDE4 could lead to derivatives endowed with a better safety profile, showing limited side-effects. In this context, thieno[3,2-d]pyrimidin-4(3H)-one-based compounds have been recently studied as a series of potent phosphodiesterase type 7 (PDE7) inhibitors, most of them being selective over other PDE enzymes, such as PDE4B. This work describes a computational study based on docking calculations followed by Comparative Molecular Fields Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA), in order to better elucidate the pharmacophore features of this series of PDE7 inhibitors. The results reveal the ligand-based approach as a promising strategy to better investigate the potency and selectivity issues of PDE7 inhibitors. In addition, the results also allowed robust statistical models able to predict the potency and selectivity trend of new analogues prior to synthesis to be obtained.

There is mounting evidence that noncoding microRNAs (miRNA) are modulated by select chemoprotective dietary agents. For example, recently we demonstrated that the unique combination of dietary fish oil (containing n - 3 fatty acids) plus pectin (fermented to butyrate in the colon) (FPA) up-regulates a subset of putative tumor suppressor miRNAs in intestinal mucosa, and down-regulates their predicted target genes following carcinogen exposure as compared to control (corn oil plus cellulose (CCA)) diet. To further elucidate the biological effects of diet and carcinogen modulated miR's in the colon, we verified that miR-26b and miR-203 directly target PDE4B and TCF4, respectively. Since perturbations in adult stem cell dynamics are generally believed to represent an early step in colon tumorigenesis and to better understand how the colonic stem cell population responds to environmental factors such as diet and carcinogen, we additionally determined the effects of the chemoprotective FPA diet on miRNAs and mRNAs in colonic stem cells obtained from Lgr5-EGFP-IRES-creER(T2) knock-in mice. Following global miRNA profiling, 26 miRNAs (P < 0.05) were differentially expressed in Lgr51(high) stem cells as compared to Lgr5(negative) differentiated cells. FPA treatment up-regulated miR-19b, miR-26b and miR-203 expression as compared to CCA specifically in Lgr5(high) cells. In contrast, in Lgr5(negative) cells, only miR-19b and its indirect target PTK2B were modulated by the FPA diet. These data indicate for the first time that select dietary cues can impact stem cell regulatory networks, in part, by modulating the steady-state levels of miRNAs. To our knowledge, this is the first study to utilize Lgr5 reporter mice to determine the impact of diet and carcinogen on miRNA expression in colonic stem cells and their progeny. (C) 2015 Elsevier B.V. All rights reserved.