ArticleJournal of medicinal chemistry2014
Discovery of a phosphodiesterase 9A inhibitor as a potential hypoglycemic agent.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 75 citations in OpenAlex.
- Structure-Guided Optimization of PDE9A Inhibitors Tackling Neuroinflammation: A Combined Computational and In Vitro Study.ChemMedChem · 2026Article
- Novel Phosphodiesterase‑2 Inhibitors Discovered via Structure-Based Virtual Screening Targeting the Allosteric GAF‑B Domain.ACS medicinal chemistry letters · 2026Article
- Chemical Space Exploration and Machine Learning-Based Screening of PDE7A Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Phosphodiesterase 9A inhibition improves aging-related increase in pulmonary vascular resistance in mice.GeroScience · 2024Article
- Synthesis,Antidiabetic and Antitubercular Evaluation of Quinoline-pyrazolopyrimidine hybrids and Quinoline-4-Arylamines.ChemistryOpen · 2024Article
- A Review of Antidiabetic Medicinal Plants as a Novel Source of Phosphodiesterase Inhibitors: Future Perspective of New Challenges Against Diabetes Mellitus.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2024Review
- A Homogeneous Bioluminescent System to Monitor Cyclic Guanosine Monophosphate.ACS pharmacology & translational science · 2023Article
- Virtual Screening-Accelerated Discovery of a Phosphodiesterase 9 Inhibitor with Neuroprotective Effects in the Kainate Toxicity In Vitro Model.ACS chemical neuroscience · 2023Article
- Discovery of Novel Tryptanthrin Derivatives with Benzenesulfonamide Substituents as Multi-Target-Directed Ligands for the Treatment of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- BAY-7081: A Potent, Selective, and Orally Bioavailable Cyanopyridone-Based PDE9A Inhibitor.Journal of medicinal chemistry · 2022Article
- Discovery of Dipyridamole Analogues with Enhanced Metabolic Stability for the Treatment of Idiopathic Pulmonary Fibrosis.Molecules (Basel, Switzerland) · 2022Article
- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- Deciphering the potential role of Maca compounds prescription influencing gut microbiota in the management of exercise-induced fatigue by integrative genomic analysis.Frontiers in nutrition · 2022Article
- Selectivity mechanism of phosphodiesterase isoform inhibitor through in silico investigations.Journal of molecular modeling · 2021Article
- Pyrrolotriazinone as an Underexplored Scaffold in Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems.Biomolecules · 2021Article
- A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Role of Phosphodiesterase in the Biology and Pathology of Diabetes.International journal of molecular sciences · 2020Review
- Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Phosphodiesterase 9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of diabetes and Alzheimer's disease. Here we report a potent PDE9 inhibitor 3r that has an IC50 of 0.6 nM and >150-fold selectivity over other PDEs. The HepG2 cell-based assay shows that 3r inhibits the mRNA expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase. These activities of 3r, together with the reasonable pharmacokinetic properties and no acute toxicity at 1200 mg/kg dosage, suggest its potential as a hypoglycemic agent. The crystal structure of PDE9-3r reveals significantly different conformation and hydrogen bonding pattern of 3r from those of previously published 28s. Both 3r and 28s form a hydrogen bond with Tyr424, a unique PDE9 residue (except for PDE8), but 3r shows an additional hydrogen bond with Ala452. This structure information might be useful for design of PDE9 inhibitors.
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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.