ArticleMolecular pharmacology2008
Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil.
Article in Molecular pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 55 citations in OpenAlex.
- Disarming Pseudomonas aeruginosa: repurposing vardenafil, valsartan, and olmesartan as anti-virulence and antibiofilm agents.Scientific reports · 2026Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Coupling of conformational dynamics and inhibitor binding in the phosphodiesterase-5 family.Protein science : a publication of the Protein Society · 2023Article
- Histone deacetylase inhibitors synergize with sildenafil to suppress purine metabolism and proliferation in pulmonary hypertension.Vascular pharmacology · 2023Article
- Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine.Life (Basel, Switzerland) · 2023Article
- Phosphodiesterase Type 5 Inhibitors Greatly Affect Physicochemical Properties of Model Lipid Membranes.Membranes · 2021Article
- A synthetic mimic of phosphodiesterase type 5 based on corona phase molecular recognition of single-walled carbon nanotubes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Identification of New Targets and the Virtual Screening of Lignans against Alzheimer's Disease.Oxidative medicine and cellular longevity · 2020Article
- Exploration of icariin analog structure space reveals key features driving potent inhibition of human phosphodiesterase-5.PloS one · 2019Article
- Article
- Investigation of PDE5/PDE6 and PDE5/PDE11 selective potent tadalafil-like PDE5 inhibitors using combination of molecular modeling approaches, molecular fingerprint-based virtual screening protocols and structure-based pharmacophore development.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair.International journal of molecular sciences · 2017Review
- Structural Asymmetry of Phosphodiesterase-9A and a Unique Pocket for Selective Binding of a Potent Enantiomeric Inhibitor.Molecular pharmacology · 2015Article
- Advances in targeting cyclic nucleotide phosphodiesterases.Nature reviews. Drug discovery · 2014Review
- Identification of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6.The Journal of biological chemistry · 2012Article
- Biological and structural characterization of Trypanosoma cruzi phosphodiesterase C and Implications for design of parasite selective inhibitors.The Journal of biological chemistry · 2012Article
- Distinct allostery induced in the cyclic GMP-binding, cyclic GMP-specific phosphodiesterase (PDE5) by cyclic GMP, sildenafil, and metal ions.The Journal of biological chemistry · 2011Article
- Insight into binding of phosphodiesterase-9A selective inhibitors by crystal structures and mutagenesis.Journal of medicinal chemistry · 2010Article
- Interactions between cyclic nucleotide phosphodiesterase 11 catalytic site and substrates or tadalafil and role of a critical Gln-869 hydrogen bond.The Journal of pharmacology and experimental therapeutics · 2009Article
- Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity.Biochemistry · 2008Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Vardenafil has higher affinity to phosphodiesterase-5 (PDE5) than sildenafil and lower administered dosage for the treatment of erectile dysfunction. However, the molecular basis for these differences is puzzling because two drugs have similar chemical structures. Reported here is a crystal structure of the fully active and nonmutated PDE5A1 catalytic domain in complex with vardenafil. The structure shows that the conformation of the H-loop in the PDE5A1-vardenafil complex is different from those of any known structures of the unliganded PDE5 and its complexes with the inhibitors. In addition, the molecular configuration of vardenafil differs from that of sildenafil when bound to PDE5. It is noteworthy that the binding of vardenafil causes loss of the divalent metal ions that have been observed in all the previously published PDE structures. The conformational variation of both PDE5 and the inhibitors provides structural insight into the different potencies of the drugs.
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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.