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Acetylcholinesterase (AChE) inhibitors block the enzyme that breaks down acetylcholine at cholinergic synapses. By ending acetylcholine signaling within milliseconds, AChE controls transmission in the brain and at the neuromuscular junction. The 1991 crystal structure of AChE from Torpedo californica showed the active site at the base of a deep, narrow gorge. AChE also has non-catalytic roles, which broaden its interest beyond synaptic transmission. Inhibitors here include donepezil hydrochloride and galanthamine hydrobromide, which are reversible inhibitors. The carbamates rivastigmine tartrate and neostigmine bromide, used in studies of cholinergic signaling and neurodegeneration, are also listed.
Synonyms: S 9977
Stacofylline hydrochloride is a potent inhibitor of acetylcholinesterase (AChE) with an IC50 range of 5-50 nM. This xanthine derivative exhibits notable anti-amnesic and promnesic effects, making it relevant for research into memory enhancement and cognitive function. Its pharmacological properties position it as a valuable tool in Alzheimer's disease studies and other neurological research applications.
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Synonyms: Decaffeoylverbascoside; Verbasoside
Decaffeoylacteoside is an inhibitor targeting acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and lipoxygenase (LOX). This compound exhibits moderate inhibitory activity, making it relevant for research into neurodegenerative diseases and inflammation. Its ability to modulate these enzymes provides potential applications in pharmacological studies aimed at developing therapeutic agents for conditions involving cholinergic dysregulation and oxidative stress.
AChE-IN-15 is a reversible inhibitor of human acetylcholinesterase (huAChE) with an IC50 value of 6.8 μM and human butyrylcholinesterase (huBChE) with an IC50 value of 16.1 μM. This compound exhibits significant antioxidant activity and has potential applications in research related to Alzheimer's disease. AChE-IN-15 is a valuable tool for investigating cholinesterase inhibition and its role in neurodegeneration.
AChE-IN-36 is a potent inhibitor of acetylcholinesterase, exhibiting an IC50 of 0.04 μM. This compound influences reactive oxygen species (ROS) levels and modulates the gene expression of NRF2, making it a valuable tool for studies on neurodegenerative diseases and oxidative stress responses. Its activity is relevant for research focused on cholinergic signaling and cellular antioxidant pathways.
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Ostruthol is a coumarin compound that functions as a potent inhibitor of acetylcholinesterase (AChE). This inhibition contributes to increased levels of acetylcholine, a neurotransmitter that may be diminished in neurodegenerative disorders. Ostruthol is primarily utilized in Alzheimer's disease research to explore its potential therapeutic effects and mechanisms of action.
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AChE-IN-20 is a potent acetylcholinesterase (AChE) inhibitor, demonstrating an IC50 value of 397.32 nM and a Ki value of 335.76 nM. In addition to its primary target, AChE-IN-20 exhibits significant inhibitory activity against human carbonic anhydrases I and II, and α-glucosidase, with IC50 values of 84.14 nM, 69.24 nM, and 52.08 nM, respectively. This compound is valuable for research into neurodegenerative diseases and enzymatic regulation, providing insights into potential therapeutic strategies.
2,3,9,10-Tetrahydroxyberberine bromide is a potent acetylcholinesterase (AChE) inhibitor with an IC50 value of 7.8 μM. This compound also demonstrates significant free radical scavenging activity, as evidenced by an IC50 of 43 μM in the DPPH assay. It is particularly relevant for studies focusing on Alzheimer's disease research and the exploration of neuroprotective mechanisms.
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Synonyms: 4,5-Dihydroxytetralone; 4-Hydroxy-α-tetralone
(Rac)-Sclerone is an acetylcholinesterase (AChE) inhibitor derived from the green husk of Carya illinoinensis. It demonstrates significant AChE inhibition with an IC50 value of 192.65 ± 10.12 μg/mL. This compound is utilized in research applications targeting Alzheimer's disease and other neurodegenerative disorders, where modulation of cholinergic activity is of interest.
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Epi-galantamine is a diastereomer of galantamine that functions as an acetylcholinesterase (AChE) inhibitor, demonstrating an EC50 of 45.7 μM. This alkaloid is extracted from the bulbs and flowers of Caucasian snowdrop (Galanthus woronowii). Epi-galantamine is notably utilized in research exploring neurodegenerative diseases and cognitive enhancement, contributing to studies on cholinergic signaling and potential therapeutic interventions.
AChE-IN-41 is a cholinesterase inhibitor designed to enhance acetylcholine levels by preventing its breakdown. This hybrid compound of Galantamine and Memantine demonstrates significant inhibition of cholinesterase activity, offering valuable insights for neurological research. AChE-IN-41 exhibits enhanced plasma stability and similar microsomal stability in vitro, although it possesses a shorter half-life and faster clearance in vivo, making it suitable for studies on cholinergic signaling and potential therapeutic applications in neurodegenerative diseases.
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eeAChE-IN-1 is a potent inhibitor of cholinesterase (ChE), exhibiting an IC50 value of 23 nM. This compound is valuable for research applications related to neurodegenerative disorders and the modulation of cholinergic signaling pathways. Its efficacy in inhibiting ChE makes it a significant tool for studying acetylcholine metabolism and related biological processes.
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AChE/BChE-IN-19 is a nicotinic hydrazide derivative that acts as an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC50 values of 21.45 nM and 18.42 nM, respectively. This compound is particularly relevant for studies investigating cholinergic dysfunction in neurodegenerative diseases, such as Alzheimer's disease. Its potent inhibitory activity makes it a valuable tool for exploring therapeutic strategies targeting cholinergic pathways.
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Methyl ganoderate A acetonide is a lanostane triterpene that functions as a potent acetylcholinesterase (AChE) inhibitor, exhibiting an IC50 value of 18.35 μM. This natural compound, extracted from the fruiting bodies of Ganoderma lucidum, is utilized in research efforts focused on Alzheimer's disease (AD). Its inhibition of AChE makes it a valuable tool for investigating therapeutic strategies for cognitive decline associated with neurodegenerative disorders.
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Synonyms: (S)-Floramultine; (S)-Bechuanine; Merenderine
Floramultine ((S)-Floramultine) is a reversible inhibitor of cholinesterase (ChE), demonstrating moderate potency and selectivity for various cholinesterase isoforms. This compound, derived from plant sources, exhibits significant cholinergic activity and can be utilized in research exploring the modulation of cholinergic neurotransmission. Applications include studies related to neurodegenerative disorders and the development of therapeutic agents targeting cholinergic dysfunction.
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Isograndifoliol is a selective inhibitor of butyrylcholinesterase (BChE) with an IC50 of 0.9 μM, demonstrating moderate inhibition of acetylcholinesterase (AChE) with an IC50 of 342.9 μM. This compound exhibits vasorelaxant properties and potential anti-tumor activity. Isograndifoliol is relevant for research focused on neurodegenerative diseases, particularly in studies targeting dementia.
Synonyms: (-)-Cyclopenine
(-)-Cyclopenin is a selective acetylcholinesterase (AChE) inhibitor, exhibiting an IC50 value of 2.04 μM. This enantiomer of Cyclopenin demonstrates potent modulation of cholinesterase activity, making it a valuable tool for research into neurodegenerative diseases and cognitive function. Its capacity to regulate acetylcholine levels positions it as an important reagent for studies focused on synaptic transmission and cholinergic signaling pathways.
Heliosupine is a pyrrolizidine alkaloid that acts as an acetylcholinesterase (AChE) inhibitor, exhibiting a reported IC50 of 0.57 mM. This compound demonstrates significant biological activity by deterring generalist herbivores, making it a valuable tool in ecological and pharmacological research. Its AChE inhibitory properties may also have implications for the study of neurodegenerative diseases and chemical ecology.
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AChE-IN-47 is a potent acetylcholinesterase (AChE) inhibitor with an IC50 value of 0.24 μM. This compound effectively hinders the self-aggregation of amyloid β peptides, demonstrating neuroprotective properties. Additionally, AChE-IN-47 significantly reduces intracellular accumulation of reactive oxygen species, making it a valuable tool for research in neurodegenerative disease models and studies focused on oxidative stress.
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sEH/AChE-IN-1 is a dual inhibitor targeting soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE). This compound exhibits significant biological activity in reducing neuroinflammation and memory impairment, making it a valuable tool for studying neurodegenerative diseases. Its application is particularly relevant in Alzheimer's disease research, where it may help elucidate disease mechanisms and potential therapeutic strategies.
AChE-IN-10 is a highly effective inhibitor of acetylcholinesterase (AChE), with an IC50 value of 2.4 nM. This compound demonstrates significant neuroprotective effects by enhancing neuronal morphology and increasing cell viability, while also reducing tau phosphorylation at the S396 residue. Additionally, AChE-IN-10 has been shown to decrease amyloid aggregation in conjunction with AChE activity, making it a valuable tool for research in neurodegenerative diseases and cognitive disorders.
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BChE-IN-25 is a selective inhibitor of butyrylcholinesterase (BChE), exhibiting an inhibitory concentration (IC50) of 3.77 μM. This compound demonstrates a 22-fold selectivity for BChE over acetylcholinesterase (AChE), making it a valuable tool for research applications in neurobiology and therapeutic development targeting cholinergic dysfunction. Researchers can utilize BChE-IN-25 to investigate the role of BChE in various physiological and pathological processes.
BChE-IN-38 is a potent butyrylcholinesterase (BChE) inhibitor demonstrating impressive Ki values of 62.05 nM for human carbonic anhydrase I (hCAI), 28.78 nM for human carbonic anhydrase II (hCAII), 14.09 nM for acetylcholinesterase (AChE), and 1.15 nM for BChE. In addition to its inhibitory effects, BChE-IN-38 exhibits notable cytotoxic activity. This compound is essential for research applications focusing on neurodegenerative disorders, drug development targeting cholinergic systems, and the study of enzyme inhibition mechanisms.
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HUHS2002 is a free fatty acid derivative that primarily targets cholinesterase (ChE) to enhance α7 nicotinic acetylcholine receptor activity. This compound significantly increases whole-cell membrane currents of α7 ACh receptors expressed in Xenopus oocytes in a concentration-dependent manner, with effects reversibly blocked by the Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93. Furthermore, HUHS2002 activates CaMKII in cultured rodent hippocampal neurons, an effect also inhibited by KN-93. Additionally, HUHS2002 exhibits partial inhibition of protein phosphatase 1 (PP1) activity in a cell-free assay, suggesting its potential use in studying cholinergic signaling pathways and neuropharmacology.
Axillaridine A is an acetylcholinesterase (AChE) inhibitor derived from Sarcococca hookeriana var. digyna. It effectively inhibits the catalytic activity of AChE, making it a valuable tool in the study of neurodegenerative diseases and cognitive function. This compound has potential applications in research exploring the modulation of cholinergic signaling and therapeutic strategies for conditions such as Alzheimer's disease.
Cythioate is an organophosphorus compound that functions primarily as an insecticide and anthelmintic. It acts as an acetylcholinesterase inhibitor, disrupting neuromuscular transmission in ectoparasites, which leads to paralysis and mortality. Cythioate is utilized in agricultural and veterinary applications for the control of various pest and parasitic infestations.
