ArticleEMBO molecular medicine2018
The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.
2 registry-linked trialsAbstract read
In one paragraph
Article in EMBO molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 47 papers.
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0cells of the map it votes in
47citing papers in PubMed
–field-weighted citation impact
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.
A First-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of anle138b in Healthy Male and Female Subjects
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of anle138b, and to Characterise the Effect of Food of anle138b in Mild to Moderate Parkinson's Disease
Who cites it
47 citing papers in PubMed.
- Trial
- Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease.EMBO molecular medicine · 2026Article
- Targeted clearance of extracellular Tau using aptamer-armed monocytes alleviates neuroinflammation in mice with Alzheimer's disease.Nature biomedical engineering · 2026Article
- Small molecules modulate the biomolecular condensates and liquid‒liquid phase separation.Acta pharmaceutica Sinica. B · 2026Review
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Anle138b binds predominantly to the central cavity in lipidic Aβ₄₀ fibrils and modulates fibril formation.Nature communications · 2025Article
- Amyloid-β oligomers, curvilinear and annular assemblies, imaged by cryo-ET, cryo-EM, and AFM.Science advances · 2025Article
- The role of microalgal extracts and their combination with tamoxifen in the modulation of breast cancer immunotherapy (Review).Molecular and clinical oncology · 2025Review
- Targeting Protein Misfolding and Aggregation as a Therapeutic Perspective in Neurodegenerative Disorders.International journal of molecular sciences · 2024Review
- The structure of tyrosine-10 favors ionic conductance of Alzheimer's disease-associated full-length amyloid-β channels.Nature communications · 2024Article
- Early Diagnosis of Neurodegenerative Diseases: What Has Been Undertaken to Promote the Transition from PET to Fluorescence Tracers.Molecules (Basel, Switzerland) · 2024Review
- Large-scale gene expression changes in APP/PSEN1 and GFAP mutation models exhibit high congruence with Alzheimer's disease.PloS one · 2024Article
- Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Review
- Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease.Angewandte Chemie (International ed. in English) · 2023Review
- Mechanism of action deconvolution of the small-molecule pathological tau aggregation inhibitor Anle138b.Alzheimer's research & therapy · 2023Article
- Drug screening identifies tazarotene and bexarotene as therapeutic agents in multiple sulfatase deficiency.EMBO molecular medicine · 2023Article
- Endogenous Amyloid-formed CaFunction (Oxford, England) · 2023Article
- Soluble Aβ Oligomers Formed Channels Leading to Calcium Dysregulation.Function (Oxford, England) · 2023Article
- Controlling amyloid formation of intrinsically disordered proteins and peptides: slowing down or speeding up?Essays in biochemistry · 2022Article
Corrections and comments
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Authors and funding
28 authors.
Ana Martinez HernandezDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Hendrik UrbankeDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Alan L GillmanDepartment of Bioengineering, Materials Science and Engineering, Department of Mechanical and Aerospace Engineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-1312-047X
Joon LeeDepartment of Bioengineering, Materials Science and Engineering, Department of Mechanical and Aerospace Engineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.
Sergey RyazanovDepartment of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Hope Y AgbemenyahDepartment of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
Eva BenitoDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Gaurav JainDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Lalit KauraniDFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
Gayane GrigorianDepartment of Cellular Neurobiology, Technical University Braunschweig, Braunschweig, Germany.
Andrei LeonovDepartment of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Nasrollah Rezaei-GhalehDepartment of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Petra WilkenDFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
Fernando Teran ArceDepartment of Bioengineering, Materials Science and Engineering, Department of Mechanical and Aerospace Engineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA.
Jens WagnerGroup for Neuroimmunology and Imaging, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Martin Fuhrmann *Group for Neuroimmunology and Imaging, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Mario CaruanaDepartment of Physiology and Biochemistry, Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
Angelique CamilleriDepartment of Physiology and Biochemistry, Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
Neville VassalloDepartment of Physiology and Biochemistry, Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
Markus ZweckstetterDepartment of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Roland BenzLife Sciences and Chemistry, Jacobs University of Bremen, Bremen, Germany.
Armin GieseCenter for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich, Germany.
Anja SchneiderDFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
Martin KorteDepartment of Cellular Neurobiology, Technical University Braunschweig, Braunschweig, Germany m.korte@tu-braunschweig.de rlal@ucsd.edu cigr@nmr.mpibpc.mpg.de gregor.eichele@mpibpc.mpg.de afische2@gwdg.de.ORCID 0000-0001-6956-5913
Ratnesh LalDepartment of Bioengineering, Materials Science and Engineering, Department of Mechanical and Aerospace Engineering and Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA m.korte@tu-braunschweig.de rlal@ucsd.edu cigr@nmr.mpibpc.mpg.de gregor.eichele@mpibpc.mpg.de afische2@gwdg.de.ORCID 0000-0001-7256-126X
Christian GriesingerDepartment of NMR Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany m.korte@tu-braunschweig.de rlal@ucsd.edu cigr@nmr.mpibpc.mpg.de gregor.eichele@mpibpc.mpg.de afische2@gwdg.de.ORCID 0000-0002-1266-4344
Gregor EicheleDepartment for Genes and Behavior, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany m.korte@tu-braunschweig.de rlal@ucsd.edu cigr@nmr.mpibpc.mpg.de gregor.eichele@mpibpc.mpg.de afische2@gwdg.de.ORCID 0000-0002-2863-9127
Andre FischerDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany m.korte@tu-braunschweig.de rlal@ucsd.edu cigr@nmr.mpibpc.mpg.de gregor.eichele@mpibpc.mpg.de afische2@gwdg.de.ORCID 0000-0001-8546-1161
Funding
Amyloid ion channels to design therapeutics for neurodegenerative diseasesR01AG028709 · NIA · UNIVERSITY OF CHICAGO · PI LAL, RATNESHWAR · 2006 to 2018
$3.6MNIA NIH HHS R01 AG028709
Abstract
Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level, we provide evidence that anle138b blocks the activity of conducting Aβ pores without changing the membrane embedded Aβ-oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD-related pathology that should be investigated further.
Indexed as
Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBenzodioxolesDisease Models, AnimalHippocampusMaleMiceMice, Inbred C57BLNeuronal PlasticityPhenotypePyrazolesSpatial MemoryTranscriptome3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazoleAmyloid beta-PeptidesBenzodioxolesPyrazolesAlzheimer's diseaseamyloid pathologyAβ channelsgene expressionmembrane pores
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LicenceCC BY
Read underepoch 390
Registered trials
NCT04208152ClinicalTrials.gov
NCT04685265ClinicalTrials.gov
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.