ArticleJournal of medicinal chemistry2010
Insight into binding of phosphodiesterase-9A selective inhibitors by crystal structures and mutagenesis.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
9 citing papers in PubMed, 22 citations in OpenAlex.
- Structure-Guided Optimization of PDE9A Inhibitors Tackling Neuroinflammation: A Combined Computational and In Vitro Study.ChemMedChem · 2026Article
- Review
- Article
- Shifting the paradigm in treating multi-factorial diseases: polypharmacological co-inhibitors of HDAC6.RSC medicinal chemistry · 2021Review
- Phosphodiesterase 9 (PDE9) regulates bovine tracheal smooth muscle relaxation.The Journal of veterinary medical science · 2018Article
- Structural Asymmetry of Phosphodiesterase-9A and a Unique Pocket for Selective Binding of a Potent Enantiomeric Inhibitor.Molecular pharmacology · 2015Article
- Discovery of a phosphodiesterase 9A inhibitor as a potential hypoglycemic agent.Journal of medicinal chemistry · 2014Article
- Structure-based discovery of highly selective phosphodiesterase-9A inhibitors and implications for inhibitor design.Journal of medicinal chemistry · 2012Article
- Structural asymmetry of phosphodiesterase-9, potential protonation of a glutamic acid, and role of the invariant glutamine.PloS one · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
PDE9 inhibitors have been studied as therapeutics for treatment of cardiovascular diseases, diabetes, and neurodegenerative disorders. To illustrate the inhibitor selectivity, the crystal structures of the PDE9A catalytic domain in complex with the enantiomers of PDE9 inhibitor 1-(2-chlorophenyl)-6-(3,3,3-trifluoro-2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidine-4(5H)-one ((R)-BAY73-6691 or (S)-BAY73-6691, 1r or 1s) were determined and mutagenesis was performed. The structures showed that the fluoromethyl groups of 1r and 1s had different orientations while the other parts of the inhibitors commonly interacted with PDE9A. These differences may explain the slightly different affinity of 1r (IC(50) = 22 nM) and 1s (IC(50) = 88 nM). The mutagenesis experiments revealed that contribution of the binding residues to the inhibitor sensitivity varies dramatically, from few-fold to 3 orders of magnitude. On the basis of the crystal structures, a hypothesized compound that simulates the recently published PDE9 inhibitors was modeled to provide insight into the inhibitor selectivity.
Indexed as
Identifiers
What OpenQuestion holds
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.