{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Demirbas D"],"funding":["NIGMS NIH HHS"],"pagination":["e71279"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3743849"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(8)"],"pubmed_abstract":["A cell-based high-throughput screen (HTS) was developed to detect phosphodiesterase 8 (PDE8) and PDE4/8 combination inhibitors. By replacing the Schizosaccharomyces pombe PDE gene with the murine PDE8A1 gene in strains lacking adenylyl cyclase, we generated strains whose protein kinase A (PKA)-stimulated growth in 5-fluoro orotic acid (5FOA) medium reflects PDE8 activity. From our previously-identified PDE4 and PDE7 inhibitors, we identified a PDE4/8 inhibitor that allowed us to optimize screening conditions. Of 222,711 compounds screened, ∼0.2% displayed composite Z scores of >20. Additional yeast-based assays using the most effective 367 compounds identified 30 candidates for further characterization. Among these, compound BC8-15 displayed the lowest IC₅₀ value for both PDE4 and PDE8 inh"],"journal":["PloS one"],"pubmed_title":["A yeast-based chemical screen identifies a PDE inhibitor that elevates steroidogenesis in mouse Leydig cells via PDE8 and PDE4 inhibition."],"pmcid":["PMC3743849"],"funding_grant_id":["R01GM083926-05","R21GM079662","R21 GM079662","R01 GM083926"],"pubmed_authors":["Cakici O","Demirbas D","Wyman AR","Shimizu-Albergine M","Beavo JA","Hoffman CS"],"additional_accession":[]},"is_claimable":false,"name":"A yeast-based chemical screen identifies a PDE inhibitor that elevates steroidogenesis in mouse Leydig cells via PDE8 and PDE4 inhibition.","description":"A cell-based high-throughput screen (HTS) was developed to detect phosphodiesterase 8 (PDE8) and PDE4/8 combination inhibitors. By replacing the Schizosaccharomyces pombe PDE gene with the murine PDE8A1 gene in strains lacking adenylyl cyclase, we generated strains whose protein kinase A (PKA)-stimulated growth in 5-fluoro orotic acid (5FOA) medium reflects PDE8 activity. From our previously-identified PDE4 and PDE7 inhibitors, we identified a PDE4/8 inhibitor that allowed us to optimize screening conditions. Of 222,711 compounds screened, ∼0.2% displayed composite Z scores of >20. Additional yeast-based assays using the most effective 367 compounds identified 30 candidates for further characterization. Among these, compound BC8-15 displayed the lowest IC₅₀ value for both PDE4 and PDE8 inh","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013","modification":"2025-04-26T12:56:19.85Z","creation":"2019-03-26T23:15:20Z"},"accession":"S-EPMC3743849","cross_references":{"pubmed":["23967182"],"doi":["10.1371/journal.pone.0071279"]}}