- |||||||||| Cognex (tacrine) / Shionogi
Review, Journal: Chromenone: An emerging scaffold in anti-Alzheimer drug discovery. (Pubmed Central) - Aug 14, 2024 Natural chromenone, quercetin, scopoletin, esculetin, coumestrol, umbelliferone, bergapten, and methoxsalen (xanthotoxin), and synthetic chromenone hybrids comprising structures like acridine, 4-aminophenyl, 3-arylcoumarins, quinoline, 1,3,4-oxadiazole, 1,2,3-triazole, and tacrine, have been explored for their potential to combat AD...This review comprehensively explores natural, semisynthetic, and synthetic chromenone, elucidating their synthetic routes, possible mode of action/drug targets and structure-activity relationships (SAR). The acquired knowledge provides valuable insights for the development of new chromenone hybrids against AD.
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Journal, Metabolomic study: Applying Spatial Metabolomics To Investigate Age- and Drug-Induced Neurochemical Changes. (Pubmed Central) - Jul 29, 2024 An age-dependent increase in the glutamine/glutamate ratio, an indicator of glia-neuron interconnection and neurotoxicity, was detected after tacrine administration. The presented metabolic mapping approach was able to provide visualizations of the lipid signaling and neurotransmission alterations induced by early aging and can thus be beneficial to further elucidating age-related neurochemical pathways.
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Preclinical, Journal: Selenylated Analogs of Tacrine: Synthesis, in Silico and in Vitro (Pubmed Central) - Jul 10, 2024 In vitro studies elucidated the antioxidant effects of Tacrine and its selenium hybrid (TSe) in neutralizing ABTS radicals, scavenging DPPH radicals, and reducing iron ions. Additionally, the acute oral toxicity of one synthesized compound was evaluated.
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Journal: Novel diarylated tacrine derivatives: Synthesis, characterization, anticancer, antiepileptic, antibacterial, and antifungal activities. (Pubmed Central) - Apr 13, 2024 The results suggest their potential for further exploration as cancer-specific, enzyme inhibitory, and antibacterial therapeutic agents. Notably, four compounds, namely, 5,7-bis(4-(methylthio)phenyl)tacrine (3d), 5,7-bis(4-(trifluoromethoxy)phenyl)tacrine (3e), 2,4-bis(4-(trifluoromethoxy)phenyl)-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-11-amine (4e), and 6,8-dibromotacrine (3), emerged as the most promising candidates for preclinical studies.
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Journal: New N-(1,3,4-thiadiazole-2-yl)acetamide derivatives as human carbonic anhydrase I and II and acetylcholinesterase inhibitors. (Pubmed Central) - Mar 27, 2024 Only compounds 6a and 6c showed superior activity against AChE compared to the standard agent, tacrine (THA). In silico studies, including absorption, distribution, metabolism and excretion (ADME) and drug-likeness evaluation, molecular docking, molecular dynamic simulations (MDSs) and density functional theory (DFT) calculations, were compatible with the in
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Journal: Genomics and Drug Discovery Strategies: The Role of Natural Compounds and Its Receptor in Alzheimer's Disease. (Pubmed Central) - Feb 19, 2024 PTPN11 receptor with Carnosol ligand resulted in docking score (?G = -9.1 kcal/mol) w.r.t Tacrine (FDA drug) docked score (?G = -8.0 kcal/mol) followed by MD simulation. This research will aid in the identification of potential natural compounds that future researchers can use for further validation as a potential candidate drug in combating various neurodegenerative diseases highlighting AD.
- |||||||||| ifenprodil tartrate / Chiba University Hospital
Journal: Phenoxytacrine derivatives: Low-toxicity neuroprotectants exerting affinity to ifenprodil-binding site and cholinesterase inhibition. (Pubmed Central) - Feb 5, 2024 Finally, compound I-52, showing only minor affinity to AChE, was identified as a lead candidate with favorable behavioral and neuroprotective effects using open-field and prepulse inhibition tests, along with scopolamine-based behavioral and NMDA-induced hippocampal lesion models. Our data show that compound I-52 exhibits low toxicity often associated with NMDA receptor ligands, and low hepatotoxicity, often related to THA-based compounds.
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Journal, IO biomarker: Structure Modification Converts the Hepatotoxic Tacrine into Novel Hepatoprotective Analogs. (Pubmed Central) - Jan 22, 2024 Furthermore, computer-assisted simulation docking results were highly consistent with those of the observed in vivo activities. In conclusion, the designed tacrine analogs exhibited a hepatoprotective role in acute liver damage, possibly through their antioxidative, anti-inflammatory, and antifibrotic effects.
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Review, Journal: Research and progress of focused ultrasound in the treatment of Alzheimer's disease. (Pubmed Central) - Jan 8, 2024 For the past few years, some studies could use focused ultrasound combined with microvesicles to induce blood brain barrier opening and targeted drug delivery to treat Alzheimer's disease, providing new opportunities for the treatment of Alzheimer's disease. This article reviews the application research and progress of focused ultrasound in the treatment of Alzheimer's disease, in order to provide new directions and ideas for the treatment of Alzheimer's disease.
- |||||||||| Aduhelm (aducanumab) / Eisai, Biogen, Leqembi (lecanemab-irmb) / Biogen, BioArctic, Eisai, Cognex (tacrine) / Shionogi
A historical review of interventions for Alzheimer's disease (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_14220; The literature indicates that these FDA-approved pharmacological interventions have modest effects in slowing the progression and symptoms of AD.However, controversy arose in 2021 when the FDA granted accelerated approval to aducanumab, the first monoclonal antibody treatment for AD...In 2023, lecanemab, another monoclonal antibody treatment, also received FDA accelerated approval, despite criticism concerning its efficacy and safety.Nevertheless, published data suggest that pharmacological treatments for AD are effective in treating symptoms of AD...Several studies have demonstrated that behavioral lifestyle modifications, such as aerobic exercises, can be a treatment recommendation for AD. For instance, physical exercise has long been recognized to promote improved memory function and cognitive health, presumably by protecting against hippocampal volume loss in older adults.Although there are significant advancements in developing treatment recommendations for AD, further research is warranted on the efficacy of AD treatments, including both pharmacotherapy and non-pharmacotherapy options.
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Preclinical, Journal: Antioxidant, LC-MS Analysis, and Cholinesterase Inhibitory Potentials of Phoenix dactylifera Cultivar Khudari: An In Vitro Enzyme Kinetics and In Silico Study. (Pubmed Central) - Oct 28, 2023 A molecular docking study exhibited that the compounds occupied the key residues of acetylcholinesterase with ?G range between -6.91 and -9.49 kcal/mol, where MDIE has ?G: -8.67 kcal/mol, which was better than that of tacrine, ?G: -8.25 kcal/mol...These findings suggest that the aqueous extract of Khudari fruit pulp has significant antioxidant and acetylcholinesterase inhibition potentials, and its compound, MDIE, forms stably with confirmation with the target protein, though this fruit of Khudari dates can be a better functional food for the treatment of Alzheimer's disease. Further investigations are needed to fully understand the therapeutic role of this plant-based compound via in vivo study.
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Journal: Tacrine First-Phase Biotransformation and Associated Hepatotoxicity: A Possible Way to Avoid Quinone Methide Formation. (Pubmed Central) - Sep 18, 2023 The formation of Q-cysteine and Q-glutathione adducts after human liver microsome incubation was confirmed by all of the studied tacrine derivatives, but these findings were not confirmed after incubation with 3D PHH spheroids. Therefore, the presented data call into question the suggested previously hypothesized mechanism of toxicity, and the results open new avenues for chemical modifications to improve the safety of novel tacrine derivatives.
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Journal: Novel coumarin-chalcone derivatives: Synthesis, characterization, antioxidant, cyclic voltammetry, molecular modelling and biological evaluation studies as acetylcholinesterase, ?-glycosidase, and carbonic anhydrase inhibitors. (Pubmed Central) - Sep 18, 2023 Therefore, the presented data call into question the suggested previously hypothesized mechanism of toxicity, and the results open new avenues for chemical modifications to improve the safety of novel tacrine derivatives. Compounds 7c, 7e, 7g, 7i, 7j and 7l showed promising human carbonic anhydrase I inhibition compared to the standard Acetazolamide (K: 16.64
- |||||||||| RGFP966 / BioMarin, tasquinimod (ABR-215050) / Active Biotech, Ipsen, Cognex (tacrine) / Shionogi
Review, Journal: Enhancement of neural regeneration as a therapeutic strategy for Alzheimer's disease (Review). (Pubmed Central) - Aug 24, 2023 However, further evaluations need to be performed to determine the optimal treatment. The present study reviews recent interventions for enhancing adult neurogenesis and attempts to elucidate their mechanisms of action, which may provide a theoretical basis for inducing nerve regeneration to fight against AD.
- |||||||||| Aduhelm (aducanumab) / Eisai, Biogen, Leqembi (lecanemab-irmb) / Biogen, BioArctic, Eisai, Cognex (tacrine) / Shionogi
Review, Journal: Current and future therapeutic strategies for Alzheimer's disease: an overview of drug development bottlenecks. (Pubmed Central) - Aug 21, 2023 and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD.
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Journal: 1,2,3-Triazolo[4,5-b]aminoquinolines: Design, synthesis, structure, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, and molecular docking of novel modified tacrines. (Pubmed Central) - Aug 14, 2023 Our in vivo results relate its bioavailability with the therapeutic response, demonstrating that MBA121 is a promising agent to treat the cognitive decline and neurodegeneration underlying AD. Specifically, 1,2,3-triazolo[4,5-b]aminoquinolines 5bb obtained from 3-methyl-carbonitrile (3b) showed the highest AChE (IC
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Preclinical, Journal: Novel beta-lactam substituted benzenesulfonamides: in (Pubmed Central) - Aug 4, 2023 Compounds 5f, 5h and 5l were also evaluated for their ability to inhibit the MCF-7 cancer cell line proliferation and were found to have promising anticancer activity, more potent than 5-fluorouracil and cisplatin...The acceptability of the compounds based on Lipinski's and Jorgensen's rules was also estimated from the ADME/T results. These results indicate that the synthesized molecules have the potential to be developed into effective and safe inhibitors of hCAs and AChE and could be lead agents.Communicated by Ramaswamy H. Sarma.
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