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In Silico and Ex Vivo Analyses of the Inhibitory Action of the Alzheimer Drug Posiphen and Primary Metabolites with Human Acetyl- and Butyrylcholinesterase Enzymes

https://doi.org/10.1021/acsptsci.1c00200
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What this work says

Outgoing claims: the papers this work cites, builds on, or argues with.

inferredcites →https://doi.org/10.1002/alz.12185openalex-snapshot
Targeting increased levels of APP in Down syndrome: Posiphen‐mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model
inferredcites →https://doi.org/10.1002/ana.21345openalex-snapshot
Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease
inferredcites →https://doi.org/10.1002/jcc.21256openalex-snapshot
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
inferredcites →https://doi.org/10.1002/trc2.12050openalex-snapshot
Alzheimer's disease drug development pipeline: 2020
inferredcites →https://doi.org/10.1016/j.brainres.2017.09.015openalex-snapshot
(−)-Phenserine inhibits neuronal apoptosis following ischemia/reperfusion injury
inferredcites →https://doi.org/10.1016/j.cbi.2010.02.003openalex-snapshot
Protection by pyridostigmine bromide of marmoset hemi-diaphragm acetylcholinesterase activity after soman exposure
inferredcites →https://doi.org/10.1016/j.isci.2020.100866openalex-snapshot
Post-treatment with Posiphen Reduces Endoplasmic Reticulum Stress and Neurodegeneration in Stroke Brain
inferredcites →https://doi.org/10.1016/j.nbd.2019.104528openalex-snapshot
(-)-Phenserine and the prevention of pre-programmed cell death and neuroinflammation in mild traumatic brain injury and Alzheimer's disease challenged mice
inferredcites →https://doi.org/10.1016/j.trci.2017.12.001openalex-snapshot
Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics, and pharmacokinetics in the APP/PS1 mouse
inferredcites →https://doi.org/10.1016/s0026-895x(25)09906-7openalex-snapshot
Conformers of acetylcholinesterase: a mechanism of allosteric control.
inferredcites →https://doi.org/10.1016/s0026-895x(25)14802-5openalex-snapshot
Responses of Acetylcholinesterase from Torpedo marmorata to Salts and Curarizing Drugs
inferredcites →https://doi.org/10.1016/s0306-4522(01)00613-3openalex-snapshot
Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine
inferredcites →https://doi.org/10.1017/s1041610203008676openalex-snapshot
Butyrylcholinesterase: An Important New Target in Alzheimer’s Disease Therapy
inferredcites →https://doi.org/10.1021/bi00680a029openalex-snapshot
Interaction of fluorescence probes with acetylcholinesterase. Site and specificity of propidium binding
inferredcites →https://doi.org/10.1021/bi8015197openalex-snapshot
Analysis of the Reaction of Carbachol with Acetylcholinesterase Using Thioflavin T As a Coupled Fluorescence Reporter
inferredcites →https://doi.org/10.1021/jm300871xopenalex-snapshot
Structures of Human Acetylcholinesterase in Complex with Pharmacologically Important Ligands
inferredcites →https://doi.org/10.1021/jm970210vopenalex-snapshot
Total Syntheses and Anticholinesterase Activities of (3aS)-N(8)-Norphysostigmine, (3aS)-N(8)-Norphenserine, Their Antipodal Isomers, and OtherN(8)-Substituted Analogues
inferredcites →https://doi.org/10.1021/jm9800494openalex-snapshot
Syntheses and Anticholinesterase Activities of (3aS)-N,N8-Bisnorphenserine, (3aS)-N1,N8-Bisnorphysostigmine, Their Antipodal Isomers, and Other Potential Metabolites of Phenserine
inferredcites →https://doi.org/10.1034/j.1600-0404.2000.00311.xopenalex-snapshot
The experimental Alzheimer drug phenserine: preclinical pharmacokinetics and pharmacodynamics
inferredcites →https://doi.org/10.1038/nrn1035openalex-snapshot
Neurobiology of butyrylcholinesterase
inferredcites →https://doi.org/10.1042/bj20081276openalex-snapshot
Accommodation of physostigmine and its analogues by acetylcholinesterase is dominated by hydrophobic interactions
inferredcites →https://doi.org/10.1042/bj20130013openalex-snapshot
Crystal structures of human cholinesterases in complex with huprine W and tacrine: elements of specificity for anti-Alzheimer's drugs targeting acetyl- and butyryl-cholinesterase
inferredcites →https://doi.org/10.1073/pnas.0508575102openalex-snapshot
Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent
inferredcites →https://doi.org/10.1093/brain/awy132openalex-snapshot
The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease
inferredcites →https://doi.org/10.1093/emboj/cdg005openalex-snapshot
Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site
inferredcites →https://doi.org/10.1093/nar/28.1.235openalex-snapshot
The Protein Data Bank
inferredcites →https://doi.org/10.1111/cns.13274openalex-snapshot
(−)‐Phenserine tartrate (PhenT) as a treatment for traumatic brain injury
inferredcites →https://doi.org/10.1111/j.1365-2990.1978.tb00545.xopenalex-snapshot
CHANGES IN BRAIN CHOLINESTERASES IN SENILE DEMENTIA OF ALZHEIMER TYPE
inferredcites →https://doi.org/10.1124/jpet.106.112102openalex-snapshot
The Experimental Alzheimer’s Disease Drug Posiphen [(+)-Phenserine] Lowers Amyloid-β Peptide Levels in Cell Culture and Mice
inferredcites →https://doi.org/10.1126/science.1678899openalex-snapshot
Atomic Structure of Acetylcholinesterase from Torpedo californica : A Prototypic Acetylcholine-Binding Protein
inferredcites →https://doi.org/10.1136/jnnp-2012-302589openalex-snapshot
Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans
inferredcites →https://doi.org/10.1159/000047952openalex-snapshot
Advances in the Treatment of Alzheimer’s Disease: Benefits of Dual Cholinesterase Inhibition
inferredcites →https://doi.org/10.1177/0963689719854693openalex-snapshot
(-)-Phenserine Ameliorates Contusion Volume, Neuroinflammation, and Behavioral Impairments Induced by Traumatic Brain Injury in Mice
inferredcites →https://doi.org/10.1186/s13195-019-0529-5openalex-snapshot
The “rights” of precision drug development for Alzheimer’s disease
inferredcites →https://doi.org/10.1186/s40478-019-0754-yopenalex-snapshot
Intersection of pathological tau and microglia at the synapse
inferredcites →https://doi.org/10.1212/wnl.52.6.1146openalex-snapshot
A 24-week randomized trial of controlled-release physostigmine in patients with Alzheimer’s disease
inferredcites →https://doi.org/10.1371/journal.pone.0054887openalex-snapshot
Neurotrophic and Neuroprotective Actions of (−)- and (+)-Phenserine, Candidate Drugs for Alzheimer’s Disease
inferredcites →https://doi.org/10.1371/journal.pone.0099818openalex-snapshot
(-)-Phenserine Attenuates Soman-Induced Neuropathology
inferredcites →https://doi.org/10.1371/journal.pone.0156493openalex-snapshot
Cognitive Impairments Induced by Concussive Mild Traumatic Brain Injury in Mouse Are Ameliorated by Treatment with Phenserine via Multiple Non-Cholinergic and Cholinergic Mechanisms
inferredcites →https://doi.org/10.1515/revneuro-2019-0089openalex-snapshot
Amyloid-β, tau, and the cholinergic system in Alzheimer’s disease: seeking direction in a tangle of clues
inferredcites →https://doi.org/10.1517/13543784.16.7.1087openalex-snapshot
Phenserine
inferredcites →https://doi.org/10.1517/14728222.11.2.161openalex-snapshot
Targeting acetylcholinesterase to treat neurodegeneration
inferredcites →https://doi.org/10.2146/ajhp070622openalex-snapshot
Treatment of Alzheimer’s disease in the long-term-care setting
inferredcites →https://doi.org/10.2174/1389557023406610openalex-snapshot
Non-Cholinergic Pharmacotherapy Approaches to the Future Treatment of Alzheimers Disease
inferredcites →https://doi.org/10.2174/1567205012666141218140953openalex-snapshot
Amyloid-Beta Protein Clearance and Degradation (ABCD) Pathways and their Role in Alzheimer’s Disease
inferredcites →https://doi.org/10.2174/1567205015666180110120026openalex-snapshot
(-)-Phenserine and Inhibiting Pre-Programmed Cell Death: In Pursuit of a Novel Intervention for Alzheimer’s Disease
inferredcites →https://doi.org/10.2174/1567205054367829openalex-snapshot
An Overview of Phenserine Tartrate, A Novel Acetylcholinesterase Inhibitor for the Treatment of Alzheimers Disease
inferredcites →https://doi.org/10.2174/1567205054367838openalex-snapshot
Cholinesterases: Roles in the Brain During Health and Disease
inferredcites →https://doi.org/10.2174/156720505774330564openalex-snapshot
Anticholinesterase and Pharmacokinetic Profile of Phenserine in Healthy Elderly Human Subjects
inferredcites →https://doi.org/10.2174/1871523011312020003openalex-snapshot
Synthesis of the Alzheimer Drug Posiphen into its Primary Metabolic Products (+)-N1-norPosiphen, (+)-N8-norPosiphen and (+)-N1, N8-bisnorPosiphen, their Inhibition of Amyloid Precursor Protein, α -Synuclein Synthesis, Interleukin-1β Release, and Cholinergic Action.
inferredcites →https://doi.org/10.2174/1871527313666141023141545openalex-snapshot
Status of Acetylcholinesterase and Butyrylcholinesterase in Alzheimer's Disease and Type 2 Diabetes Mellitus
inferredcites →https://doi.org/10.3233/jad-140219openalex-snapshot
Cholinesterase Inhibition in Alzheimer's Disease: Is Specificity the Answer?
inferredcites →https://doi.org/10.3233/jad-2010-101311openalex-snapshot
Phenserine Efficacy in Alzheimer's Disease
inferredcites →https://doi.org/10.3389/fneur.2019.01312openalex-snapshot
New Insights Into the Pathogenesis of Alzheimer's Disease
inferredcites →https://doi.org/10.3389/fnins.2021.635483openalex-snapshot
Drug Repurposing in the Treatment of Traumatic Brain Injury
inferredcites →https://doi.org/10.3390/biom11040580openalex-snapshot
A Comprehensive Review of Cholinesterase Modeling and Simulation
inferredcites →https://doi.org/10.3390/diseases9020029openalex-snapshot
Cholinergic Modulation of the Immune System in Neuroinflammatory Diseases
inferredcites →https://doi.org/10.3390/molecules25245789openalex-snapshot
Comprehensive Review on Alzheimer’s Disease: Causes and Treatment

What points at this work

Incoming claims: where this work appears in other papers’ reference lists and arguments.

inferred← citeshttps://doi.org/10.2139/ssrn.4633265openalex-extracted
Carltonine-Derived Compounds for Targeted Butyrylcholinesterase Inhibition
inferred← citeshttps://doi.org/10.1002/ffj.70126openalex-snapshot
Oleanolic Acid Inhibits Acetylcholinesterase and Butyrylcholinesterase Through Gorge‐Dependent Allosteric Mechanisms: An Integrated Kinetic and Molecular Dynamics Study
inferred← citeshttps://doi.org/10.1016/j.ejmech.2022.114606openalex-snapshot
Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease
inferred← citeshttps://doi.org/10.1016/j.ejphar.2025.177520openalex-snapshot
Exploring Alzheimer's disease treatment: Established therapies and novel strategies for future care
inferred← citeshttps://doi.org/10.1016/j.lfs.2024.122651openalex-snapshot
Exploring the intricacies of calcium dysregulation in ischemic stroke: Insights into neuronal cell death and therapeutic strategies
inferred← citeshttps://doi.org/10.1016/j.phrs.2023.106845openalex-snapshot
Lynx1 and the family of endogenous mammalian neurotoxin-like proteins and their roles in modulating nAChR function
inferred← citeshttps://doi.org/10.1016/j.pnpbp.2026.111640openalex-snapshot
Alzheimer's disease: Current therapeutic strategies and emerging perspectives for multifactorial intervention
inferred← citeshttps://doi.org/10.1021/acs.analchem.3c00974openalex-snapshot
Dual-Mode Ratiometric Electrochemical and Turn-On Fluorescent Detection of Butyrylcholinesterase Utilizing a Single Probe for the Diagnosis of Alzheimer’s Disease
inferred← citeshttps://doi.org/10.1021/acs.joc.5c03086openalex-snapshot
Total Synthesis of Indoline-Based Natural Products and Their Analogues
inferred← citeshttps://doi.org/10.1039/d4md00060aopenalex-snapshot
Carltonine-derived compounds for targeted butyrylcholinesterase inhibition
inferred← citeshttps://doi.org/10.1039/d5np00031aopenalex-snapshot
Natural product-derived compounds in clinical trials and drug approvals
inferred← citeshttps://doi.org/10.1080/07391102.2023.2238068openalex-snapshot
In silico exploration of promising heterocyclic molecules against both acetylcholinesterase and butyrylcholinesterase enzymes
inferred← citeshttps://doi.org/10.1155/tswj/7213377openalex-snapshot
The Eco‐Friendly Preparation of Se, Zn, and Ag MONPs and Their Current Medical Applications and Drug Delivery for AD Diseases
inferred← citeshttps://doi.org/10.1186/s13195-024-01490-zopenalex-snapshot
A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease
inferred← citeshttps://doi.org/10.1208/s12249-024-02903-wopenalex-snapshot
Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine
inferred← citeshttps://doi.org/10.6084/m9.figshare.26743661openalex-snapshot
Additional file 1 of A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease
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