ArticleChemical science2015
Computational discovery and experimental verification of tyrosine kinase inhibitor pazopanib for the reversal of memory and cognitive deficits in rat model neurodegeneration.
Article in Chemical science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 32 citations in OpenAlex.
- Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial.Hypertension (Dallas, Tex. : 1979) · 2021Trial
- Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.Inflammopharmacology · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Estimating the Similarity between Protein Pockets.International journal of molecular sciences · 2022Review
- Perspectives on the landscape and flux theory for describing emergent behaviors of the biological systems.Journal of biological physics · 2022Review
- A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs).PLoS computational biology · 2018Article
- Evolution of In Silico Strategies for Protein-Protein Interaction Drug Discovery.Molecules (Basel, Switzerland) · 2018Review
- Pazopanib Reduces Phosphorylated Tau Levels and Alters Astrocytes in a Mouse Model of Tauopathy.Journal of Alzheimer's disease : JAD · 2017Article
- Probing Origin of Binding Difference of inhibitors to MDM2 and MDMX by Polarizable Molecular Dynamics Simulation and QM/MM-GBSA Calculation.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cognition and memory impairment are hallmarks of the pathological cascade of various neurodegenerative disorders. Herein, we developed a novel computational strategy with two-dimensional virtual screening for not only affinity but also specificity. We integrated the two-dimensional virtual screening with ligand screening for 3D shape, electrostatic similarity and local binding site similarity to find existing drugs that may reduce the signs of cognitive deficits. For the first time, we found that pazopanib, a tyrosine kinase inhibitor marketed for cancer treatment, inhibits acetylcholinesterase (AchE) activities at sub-micromolar concentration. We evaluated and compared the effects of intragastrically-administered pazopanib with donepezil, a marketed AchE inhibitor, in cognitive and behavioral assays including the novel object recognition test, Y maze and Morris water maze test. Surprisingly, we found that pazopanib can restore memory loss and cognitive dysfunction to a similar extent as donepezil in a dosage of 15 mg kg
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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.