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hAChE-IN-1 (Compound 24) is a potent inhibitor of human acetylcholinesterase (hAChE), with an inhibition concentration half-maximum (IC50) of 1.09 μM, and inhibits tau-oligomerization with an effective concentration half-maximum (EC50) of 2.71 μM as determined by a cellular tau fluorescence resonance energy transfer (FRET) assay [1].

hAChE-IN-3 (compound 5c) serves as a potent inhibitor for AChE, BuChE, MAO-B, and BACE-1, with respective IC50 values of 0.44, 0.08, 5.15, and 0.38 μM, demonstrating its ability to cross the blood-brain barrier. This compound also exhibits antioxidant properties and metal chelation capabilities. Additionally, it targets peripheral anion sites, potentially modulating β-amyloid and ameliorating neurodegeneration linked to Alzheimer's disease, highlighting its research potential for this condition [1].

hAChE-IN-6 (compound 51) is a brain-penetrant acetylcholinesterase (AChE) inhibitor with an IC50 of 0.16 μM. It also inhibits human butyrylcholinesterase (hBuChE) and glycogen synthase kinase 3 beta (GSK3β), with IC50 values of 0.69 μM and 0.26 μM, respectively. Additionally, hAChE-IN-6 impedes the self-aggregation of tau protein and amyloid-beta 1-42 (Aβ1-42), making it useful for Alzheimer's disease (AD) research [1].

hAChE-IN-7 (compound 5s) serves as a mixed inhibitor impacting both the catalytic active site (CAS) and peripheral anionic site (PAS) of hAChE. This compound demonstrates a balanced inhibitory effect with IC 50 values of 69.8 nM for hAChE and 68.0 nM for hBuChE. Additionally, it exhibits an inhibitory activity against β-secretase-1 (BACE-1) with an IC 50 of 3.6 μM. hAChE-IN-7 holds potential for research in Alzheimer's disease (AD) [1].

hAChE-IN-2, a potent inhibitor of human acetylcholinesterase (hAChE), exhibits an inhibitory concentration 50 (IC50) of 0.71 μM and additionally impedes tau-oligomerization with an effective concentration 50 (EC50) of 2.21 μM, demonstrating neuroprotective activity [1].

hAChE-IN-5 (compound 49) is a dual inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBuChE), showing IC50 values of 0.17 μM for both enzymes. It also potently inhibits glycogen synthase kinase 3 beta (GSK3β) with an IC50 of 0.21 μM. Furthermore, it effectively inhibits tau protein and Aβ1-42 peptide self-aggregation, and can bind the peripheral anionic site (PAS) to prevent amyloid-beta (Aβ)-induced neurotoxicity. hAChE-IN-5's ability to cross the blood-brain barrier (BBB) supports its potential in developing multitargeted anti-Alzheimer's agents [1].

Compound AK-2, also known as hAChE hBACE-1-IN-4, is a quinazoline derivative that demonstrates significant inhibitory activity against the enzymes hAChE and hBACE-1 (hAChE, IC 50 = 0.283 μM; hBACE-1, IC 50 = 0.231 μM). This compound also shows potential in inhibiting Aβ aggregation and possesses characteristics such as non-neurotoxicity, blood-brain barrier permeability, and oral activity, making it a valuable agent for research in Alzheimer's disease [1].

Compd 5d (hAChE-IN-4) is a potent hAChE inhibitor that readily crosses the blood-brain barrier, exhibiting an IC50 of 0.25 μM, and is utilized in the study of Alzheimer's disease [1].

Compound 16 (hAChE/Aβ1-42-IN-1) is a potent inhibitor targeting both hAChE and Aβ1-42 aggregation, demonstrating considerable safety in hepG2 cell lines and excellent brain-blood barrier (BBB) penetration with a broad safety margin. This compound shows promise for Alzheimer's disease (AD) research [1].

Donepezil (Aricept) is a piperidine-based, potent, specific, and reversible inhibitor of acetylcholinesterase (AChE). It can be used for the treatment of mild to moderate dementia of the Alzheimer's type.

Donepezil HCl(Aricept) is a selective and effective AChE inhibitor for bAChE and hAChE (IC50: 8.12 11.6 nM).

AChE BChE MAO-B-IN-1 is a reversible, non-time-dependent inhibitor of AChE, BChE, and MAO-B that crosses the blood-brain barrier, exhibiting inhibitory effects on hAChE, hBChE, and hMAO-B with IC50s of 7.31, 0.56, and 26.1 μM, respectively. [AChE BChE MAO-B-IN-1] had a neuroprotective effect and was not significantly cytotoxic.

AChE BChE-IN-9 (Compound 7a) is a potent, orally active inhibitor of AChE and BChE, with IC50 values of 5.74 μM and 14.05 μM against hAChE and eqBChE, respectively. It also demonstrates effective antioxidant activity (IC50 = 57.35 μM), chelates iron, and modulates amyloid β 1-42 aggregation. Notably, AChE-IN-16 can cross the blood-brain barrier [1].

sEH/AChE-IN-3 (15) serves as a dual inhibitor targeting both soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE), demonstrating potent activity and the ability to cross the blood-brain barrier (BBB). It exhibits IC50 values of 0.4 nM for human sEH (hsEH), 1.94 nM for human AChE (hAChE), 615 nM for human butyrylcholinesterase (hBChE), 4.3 nM for mouse sEH (msEH), and 2.61 nM for mouse AChE (mAChE), indicating its efficacy across these enzymes.

AChE BChE-IN-1 is a potent dual inhibitor of acetylcholinesterase and butyrylcholinesterase with blood-brain barrier permeability, exhibiting IC50 values of 1.06 nM for hAChE and 7.3 nM for hBChE, and showing antioxidant effects. AChE BChE-IN-1 can be used in Alzheimer's disease research.

BChE-IN-5 is a potent and selective inhibitor of BChE (IC50: 2.8 nM) with a higher inhibitory effect on hBChE than hAChE and potential applications in Alzheimer's disease research.

AChE BChE BACE-1-IN-2 (Compound 4o) is an orally active AChE, BACE-1, and BChE inhibitor with IC50 values of 0.069, 0.097, and 0.127 μM against hAChE, hBACE-1, and hBChE, respectively. It exhibits remarkable antioxidant potential, considerable binding capability towards PAS-AChE, potential disassembly of Aβ aggregates, and neuroprotective activity against Aβ-induced stress with excellent brain permeation [1].

PD07 is an orally active acetylcholinesterase (AChE) inhibitor, exhibiting an IC50 of 0.29 μM against human AChE, and demonstrates inhibition of cholinesterases (ChEs), β-site amyloid precursor protein cleaving enzyme 1 (BACE1) with an IC50 of 13.42 μM, as well as Aβ1–42 aggregation in vitro. Additionally, PD07 possesses antioxidant properties with a DPPH radical inhibition IC50 value of 26.46 μM and has been shown to ameliorate memory and cognitive deficits in scopolamine-induced amnesic rats. This compound is relevant for Alzheimer’s disease research [1].

SD-6, an orally active inhibitor targeting both hAChE and hBChE, demonstrates IC50 values of 0.907 µM and 1.579 µM, respectively. With its excellent blood-brain barrier (BBB) permeability and lack of neurotoxicity, SD-6 holds potential for Alzheimer's disease research.

AChE-IN-24 is a potent inhibitor of AChE that crosses the blood-brain barrier, strongly inhibiting hAChE (IC50: 0.053 μM). AChE-IN-24 can be used to study Alzheimer's disease (AD).

AChE BChE-IN-4 (BMC-3) is an AChE and BChE dual inhibitor that can cross the BBB, with IC50 values for human AChE (hAChE) and human BChE (hBChE) of 792 nM and 2.2 nM, respectively[1].

AChE BChE BACE-1-IN-1 (Compound 4k) is an orally active inhibitor that targets acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), with IC50 values of 0.058 μM, 0.082 μM, and 0.115 μM against hAChE, hBChE, and hBACE-1, respectively. It exhibits significant binding affinity with PAS-AChE, excellent blood-brain barrier permeability, potential disassembly of amyloid-beta (Aβ) aggregates, neuroprotective properties against Aβ-induced stress, and remarkable antioxidant capabilities [1].

Galanthamine N-Oxide, an alkaloid extracted from Zephyranthes concolor bulbs, effectively inhibits acetylcholinesterase (AChE) from electric eel with an EC50 of 26.2 μM. It acts as a significant inhibitor of substrate accommodation within the active sites of Torpedo californica AChE (TcAChE), human AChE (hAChE), and human BChE (hBChE) enzymes.

AChE-IN-63 (Compound 5AD) serves as a selective inhibitor of hAChE, exhibiting an IC 50 value of 0.103 μM. Moreover, it inhibits hBChE and hBACE-1 with IC 50 values of 10 μM and 1.342 μM, respectively. AChE-IN-63 is effective in inhibiting Aβ aggregation and preventing the formation and deposition of Aβ1-42. It can effectively penetrate the blood-brain barrier and is orally bioavailable. This compound is primarily utilized in research related to Alzheimer's disease [1].

PD25, an inhibitor of both AChE and BuChE, demonstrates inhibitory constants of hAChE IC50: 1.58 μM, eeAChE IC50: 1.63 μM, and eqBuChE IC50: 2.39 μM. It exhibits antioxidant properties with a DPPH IC50 of 29.55 μM. This compound is utilized in the research of Alzheimer’s disease [1].

AChE-IN-29, a 3-OH pyrrolidine derivative, acts as a cholinesterase (ChE) inhibitor with potent activity against human acetylcholinesterase (hAChE), electric eel acetylcholinesterase (eeAChE), and equine butyrylcholinesterase (eqBChE), exhibiting IC50 values of 0.25 μM, 0.23 μM, and 0.72 μM, respectively. It is utilized in Alzheimer's disease research [1].

sEH/AChE-IN-4 -15 is a potent, blood-brain barrier-penetrating dual inhibitor targeting soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE). It demonstrates notable inhibition efficacy, with IC50 values of 3.1 nM (hsEH), 1660 nM (hAChE), 179 nM (hBChE, human butyrylcholinesterase), 14.5 nM (msEH), and 102 nM (mAChE), indicating its significant inhibitory action across both targeted enzymes in human and mouse models.

AChE BChE-IN-5 (BMC-16) is a dual inhibitor of AChE and BChE that can cross the BBB, with IC50 values of 266 nM for human AChE (hAChE) and 10.6 nM for human BChE (hBChE) [1].

PD10 is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), exhibiting inhibitory potency at human AChE (hAChE IC50: 0.56 μM), electric eel AChE (eeAChE IC50: 0.59 μM), and equine serum BuChE (eqBuChE IC50: 1.06 μM). It is utilized in research pertaining to Alzheimer’s disease [1].

AChE-IN-14 is a potent cholinesterase inhibitor, acting on electric eel acetylcholinesterase (eeAChE) (IC50: 0.46 μM), human recombinant acetylcholinesterase (hAChE) (IC50: 0.48 μM) and equine serum butyrylcholinesterase (eqBuChE) (IC50: 0.44 μM). AChE-IN-14 has a high affinity for the human H3 receptor (H3R) (Ki: 159.8 nM) and can be used to study Alzheimer's disease.

Dihydro Donepezil, also known as Dihydro E2020, is a metabolite derived from Donepezil. Donepezil is a highly specific and potent inhibitor of acetylcholinesterase (AChE) with IC50 values of 8.12 nM and 11.6 nM for butyrylcholinesterase (bAChE) and human acetylcholinesterase (hAChE), respectively [1].

AChE/GSK-3β-IN-1 is a potent dual AChE/GSK-3β inhibitor that crosses the blood-brain barrier and acts on hAChE (IC50: 1.2 nM), hBChE (IC50: 149.8 nM) and hGSK-3β (IC50: 22.4 nM). AChE/GSK-3β-IN-1 is able to occupy the ATP binding site of DYRK1A. aChE/GSK-3β-IN-1 exhibits high kinase selectivity for the CMGC kinase family. aChE/GSK-3β-IN-1 inhibits ROS expression and reduces oxidative stress. aChE/GSK-3β-IN-1 can be used to study Alzheimer's disease.

NDs-IN-1 (Compound 3g) is a novel non-covalent multi-target inhibitor that inhibits the activities of key enzymes such as hBACE-1, hAChE, and hMAO-B, and is primarily used in the study of neurodegenerative diseases [1].

PD24 serves as an inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), with inhibitory concentrations (IC50) of 1.72 μM for human AChE (hAChE), 1.76 μM for electric eel AChE (eeAChE), and 2.64 μM for equine serum BuChE (eqBuChE). Additionally, it exhibits antioxidant properties, demonstrated by its ability to inhibit DPPH with an IC50 of 28.72 μM. This compound is utilized in Alzheimer's disease research [1].

AChE/Nrf2 modulator 1, an orally active compound, serves as a modulator of acetylcholinesterase (AChE) and nuclear factor erythroid 2-related factor 2 (Nrf2). It exhibits Nrf2 inductive activity alongside inhibitory effects on eeAChE and hAChE, demonstrating IC 50 values of 0.07 μM and 0.38 μM, respectively. This compound is applicable in Alzheimer's disease research.

hBChE-IN-1 (compound 4), a quinolizidinyl derivative, effectively inhibits human Butyrylcholinesterase (hBChE) with an IC50 value of 7 nM, demonstrating high selectivity against human Acetylcholinesterase (hAChE). It also inhibits tau and Aβ 40 protein aggregation, with IC50 values of 20 and 4.3 μM, respectively, making it valuable for Alzheimer's disease research [1].

PCS1055 is a selective and competitive antagonist of the muscarinic M4 receptor (muscarinic M4 receptor), with an IC50 of 18.1 nM and a Kd of 5.72 nM. It inhibits the binding of the radioligand [3H]-NMS to the M4 receptor, with a Ki of 6.5 nM. Additionally, PCS1055 acts as an AChE inhibitor, exhibiting IC50 values of 22 nM for electric eel AChE and 120 nM for human AChE.