ArticleJournal of medicinal chemistry2022
Discovery and In Vivo Proof of Concept of a Highly Potent Dual Inhibitor of Soluble Epoxide Hydrolase and Acetylcholinesterase for the Treatment of Alzheimer's Disease.
Article in Journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed.
- Review
- Acetylcholinesterase as a Multifunctional Target in Amyloid-Driven Neurodegeneration: From Dual-Site Inhibitors to Anti-Agregation Strategies.International journal of molecular sciences · 2025Review
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- Inflammatory Bridges: Interconnections Between Alzheimer's Disease and Bone Health.Aging and disease · 2025Review
- Inhibitors of soluble epoxide hydrolase and cGAS/STING repair defects in amyloid-β clearance underlying vascular complications of Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- Molecular Modeling Insights on the Pharmaceuticals and Hypotheses of Alzheimer's Disease.Current medicinal chemistry · 2025Review
- Design and Synthesis of sEH/HDAC6 Dual-Targeting Inhibitors for the Treatment of Inflammatory Pain.Journal of medicinal chemistry · 2024Article
- Carltonine-derived compounds for targeted butyrylcholinesterase inhibition.RSC medicinal chemistry · 2024Article
- Acetylcholinesterase: A Versatile Template to Coin Potent Modulators of Multiple Therapeutic Targets.Accounts of chemical research · 2024Article
- Design and Synthesis of Multi-Functional Ligands through Hantzsch Reaction: Targeting CaPharmaceutics · 2024Article
- Recent Advancements in the Treatment of Alzheimer's Disease: A Multitarget-directed Ligand Approach.Current medicinal chemistry · 2024Review
- Review
- Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer's Disease Treatment.International journal of molecular sciences · 2023Article
- Tacrine-Based Hybrids: Past, Present, and Future.International journal of molecular sciences · 2023Review
- Biginelli Reaction Synthesis of Novel Multitarget-Directed Ligands with CaMolecules (Basel, Switzerland) · 2022Article
- Discovery and Optimization of Indoline-Based Compounds as Dual 5-LOX/sEH Inhibitors:Journal of medicinal chemistry · 2022Article
- A Combined Chronic Low-Dose Soluble Epoxide Hydrolase and Acetylcholinesterase Pharmacological Inhibition Promotes Memory Reinstatement in Alzheimer's Disease Mice Models.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Designing a Small Fluorescent Inhibitor to Investigate Soluble Epoxide Hydrolase Engagement in Living Cells.ACS medicinal chemistry letters · 2022Article
- Unveiling the Multitarget Anti-Alzheimer Drug Discovery Landscape: A Bibliometric Analysis.Pharmaceuticals (Basel, Switzerland) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
Abstract
With innumerable clinical failures of target-specific drug candidates for multifactorial diseases, such as Alzheimer's disease (AD), which remains inefficiently treated, the advent of multitarget drug discovery has brought a new breath of hope. Here, we disclose a class of 6-chlorotacrine (huprine)-TPPU hybrids as dual inhibitors of the enzymes soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE), a multitarget profile to provide cumulative effects against neuroinflammation and memory impairment. Computational studies confirmed the gorge-wide occupancy of both enzymes, from the main site to a secondary site, including a so far non-described AChE cryptic pocket. The lead compound displayed in vitro dual nanomolar potencies, adequate brain permeability, aqueous solubility, human microsomal stability, lack of neurotoxicity, and it rescued memory, synaptic plasticity, and neuroinflammation in an AD mouse model, after low dose chronic oral administration.
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.