ArticlePloS one2013
A yeast-based chemical screen identifies a PDE inhibitor that elevates steroidogenesis in mouse Leydig cells via PDE8 and PDE4 inhibition.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Trial
- A fission yeast-based platform for nematode PDE inhibitor discovery.Cellular signalling · 2026Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Pharmacological modulation of phosphodiesterase-7 as a novel strategy for neurodegenerative disorders.Inflammopharmacology · 2022Review
- Structure-based discovery of orally efficient inhibitorsActa pharmaceutica Sinica. B · 2022Article
- Treatment of Experimental Autoimmune Encephalomyelitis with an Inhibitor of Phosphodiesterase-8 (PDE8).Cells · 2022Article
- The Role of PDE8 in T Cell Recruitment and Function in Inflammation.Frontiers in cell and developmental biology · 2021Review
- Use of a Fission Yeast Platform to Identify and Characterize Small Molecule PDE Inhibitors.Frontiers in pharmacology · 2021Review
- A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.Cellular signalling · 2019Article
- The Distribution of Standard Deviations Applied to High Throughput Screening.Scientific reports · 2019Article
- Identification and characterization of a potent and biologically-active PDE4/7 inhibitor via fission yeast-based assays.Cellular signalling · 2017Article
- Roflumilast and aquaporin-2 regulation in rat renal inner medullary collecting duct.Physiological reports · 2017Article
- Differential Expression and Function of PDE8 and PDE4 in Effector T cells: Implications for PDE8 as a Drug Target in Inflammation.Frontiers in pharmacology · 2016Article
- A short review on structure and role of cyclic-3',5'-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool.Journal of research in pharmacy practiceReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
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 inhibition in in vitro enzyme assays. This compound also displays significant activity against PDE10A and PDE11A. BC8-15 elevates steroidogenesis in mouse Leydig cells as a single pharmacological agent. Assays using BC8-15 and two structural derivatives support a model in which PDE8 is a primary regulator of testosterone production by Leydig cells, with an additional role for PDE4 in this process. BC8-15, BC8-15A, and BC8-15C, which are commercially available compounds, display distinct patterns of activity against PDE4, PDE8, PDE10A, and PDE11A, representing a chemical toolkit that could be used to examine the biological roles of these enzymes in cell culture systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.