ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Memory enhancing effects of BPN14770, an allosteric inhibitor of phosphodiesterase-4D, in wild-type and humanized mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 73 citations in OpenAlex.
- Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial.Nature medicine · 2021Trial
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Review
- Inhibition of GRK2-PDE4D Axis Suppresses Fibroblast-Like Synoviocytes Hyperplasia and Alleviates Experimental Arthritis.International journal of biological sciences · 2025Article
- Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome.Molecular autism · 2024Article
- PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024Review
- Robust Quantification of Phosphodiesterase-4D in Monkey Brain with PET andJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024Article
- DNA methylation patterns of FKBP5 regulatory regions in brain and blood of humanized mice and humans.Molecular psychiatry · 2024Article
- Allosteric inhibition of phosphodiesterase 4D induces biphasic memory-enhancing effects associated with learning-activated signaling pathways.Psychopharmacology · 2024Article
- Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain.Genes, brain, and behavior · 2023Article
- Toxic PARP trapping upon cAMP-induced DNA damage reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer.Nature communications · 2023Article
- An Empirical Quantitative Structure-Activity Relationship Equation Assists the Discovery of High-Affinity Phosphodiesterase 4D Inhibitors as Leads to PET Radioligands.Journal of medicinal chemistry · 2023Article
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Baicalin attenuates amyloid β oligomers induced memory deficits and mitochondria fragmentation through regulation of PDE-PKA-Drp1 signalling.Psychopharmacology · 2022Article
- Article
- Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders.Molecular psychiatry · 2021Review
- Insight into Inhibitory Mechanism of PDE4D by Dietary Polyphenols Using Molecular Dynamics Simulations and Free Energy Calculations.Biomolecules · 2021Article
- Phosphodiesterase-4D Knockdown in the Prefrontal Cortex Alleviates Memory Deficits and Synaptic Failure in Mouse Model of Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
- PDE inhibition in distinct cell types to reclaim the balance of synaptic plasticity.Theranostics · 2021Review
- Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal AtrophyFrontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Inhibitors of phosphodiesterase-4 (PDE4) have beneficial effects on memory in preclinical and clinical studies. Development of these drugs has stalled due to dose-limiting side effects of nausea and emesis. While use of subtype-selective inhibitors (i.e., for PDE4A, B, or D) could overcome this issue, conservation of the catalytic region, to which classical inhibitors bind, limits this approach. The present study examined the effects of BPN14770, an allosteric inhibitor of PDE4D, which binds to a primate-specific, N-terminal region. In mice engineered to express PDE4D with this primate-specific sequence, BPN14770 was 100-fold more potent for improving memory than in wild-type mice; meanwhile, it exhibited low potency in a mouse surrogate model for emesis. BPN14770 also antagonized the amnesic effects of scopolamine, increased cAMP signaling in brain, and increased BDNF and markers of neuronal plasticity associated with memory. These data establish a relationship between PDE4D target engagement and effects on memory for BPN14770 and suggest clinical potential for PDE4D-selective 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.