ArticleCellular signalling2017
Identification and characterization of a potent and biologically-active PDE4/7 inhibitor via fission yeast-based assays.
Article in Cellular signalling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Review
- A fission yeast-based platform for nematode PDE inhibitor discovery.Cellular signalling · 2026Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Recent Advances in Medicinal Chemistry of Phosphodiesterase 7 Inhibitors and their Potential Therapeutic Applications.Recent advances in inflammation & allergy drug discovery · 2025Review
- Use of a Fission Yeast Platform to Identify and Characterize Small Molecule PDE Inhibitors.Frontiers in pharmacology · 2021Review
- Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics.Antioxidants (Basel, Switzerland) · 2020Review
- Role of Phosphodiesterase 7 (PDE7) in T Cell Activity. Effects of Selective PDE7 Inhibitors and Dual PDE4/7 Inhibitors on T Cell Functions.International journal of molecular sciences · 2020Review
- The future of bronchodilation: looking for new classes of bronchodilators.European respiratory review : an official journal of the European Respiratory Society · 2019Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.Cellular signalling · 2019Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
We previously constructed a collection of fission yeast strains that express various mammalian cyclic nucleotide phosphodiesterases (PDEs) and developed a cell-based high throughput screen (HTS) for small molecule PDE inhibitors. Here we describe a compound, BC54, that is a selective inhibitor of enzymes from the cAMP-specific PDE4 and PDE7 families. Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells. We further exploited PKA-regulated growth phenotypes in fission yeast to isolate two mutant alleles of the human PDE4B2 gene that encode enzymes possessing single amino acid changes that confer partial resistance to BC54. We confirm this resistance to both BC54 and rolipram via yeast-based assays and, for PDE4B2
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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.