ArticleJournal of medicinal chemistry2019
Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 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
- Water Networks as Hydrophobic Recognition Motifs in Proteins.Angewandte Chemie (International ed. in English) · 2026Article
- The Emerging Role of Phosphodiesterase Inhibitors in Fragile X Syndrome and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeted protein degradation of PDE4 shortforms by a novel proteolysis targeting chimera.The FEBS journal · 2025Article
- [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Review
- 3D-QSAR Studies on High-affinity Phosphodiestera.Current medicinal chemistry · 2025Article
- Inhibition of GRK2-PDE4D Axis Suppresses Fibroblast-Like Synoviocytes Hyperplasia and Alleviates Experimental Arthritis.International journal of biological sciences · 2025Article
- Drug Treatments for Neurodevelopmental Disorders: Targeting Signaling Pathways and Homeostasis.Current neurology and neuroscience reports · 2024Review
- Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome.Molecular autism · 2024Article
- Targeting cAMP signaling and phosphodiesterase 4 for liver disease treatment.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2024Article
- PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024Review
- Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile x syndrome.Research square · 2024Article
- Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Robust Quantification of Phosphodiesterase-4D in Monkey Brain with PET andJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024Article
- Allosteric inhibition of phosphodiesterase 4D induces biphasic memory-enhancing effects associated with learning-activated signaling pathways.Psychopharmacology · 2024Article
- Phosphodiesterase 2 and Its Isoform A as Therapeutic Targets in the Central Nervous System Disorders.CNS & neurological disorders drug targets · 2024Review
- Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review.Dermatology and therapy · 2023Review
- Differential effects of two phosphodiesterase 4 inhibitors against lipopolysaccharide-induced neuroinflammation in mice.BMC neuroscience · 2023Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 1 country.
Funding
Abstract
Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compounds was based on iterative analysis of X-ray crystal structures combined with metabolite identification. Selectivity for the activated, dimeric form of PDE4D provided potent memory enhancing effects in a mouse model of novel object recognition with improved tolerability and reduced vascular toxicity over earlier PDE4 inhibitors that lack subtype selectivity. The lead compound, 28 (BPN14770), has entered midstage, human phase 2 clinical trials for the treatment of Fragile X Syndrome.
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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.