aβ1-42

BF-168 is a candidate probe for PET and specifically recognizes both neuritic and diffuse plaques (Ki: 6.4 nM for Aβ1-42).

BF 227 is a candidate for an amyloid imaging probe for PET [Ki: 4.3 nM for Aβ1-42 fibrils].

PQM130 is a neuroprotective compound ,and is a potential anti-AD drug.

ChE/Aβ1-42-IN-1 (compound 28) is a potent aggregation inhibitor of ChE and Aβ1-42 with excellent BBB permeability, exhibiting IC50 values of 0.062 μM for AChE, 0.767 μM for BuChE, and 1.227 μM for Aβ1-42 aggregation. ChE/Aβ1-42-IN-1 is a potent multi-targeted anti-Alzheimer's disease agent [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].

1. Spinosin (Flavoayamenin) ameliorated memory impairment induced through AβO, the serotonergic neurotransmitter system, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of Spinosin. 2. Spinosin exerts anxiolytic-like effects, and its mechanism of action appears to be modulated by GABAA and 5-HT1A receptors. 3. There was a wide brain regional tissue distribution of Spinosin. The concentrations of Spinosin in corpus striatum and hippocampus were higher than that in other areas.

Aβ1–42 aggregation inhibitor 2 (compound 7c) is a potent inhibitor of Aβ1-42 aggregation, playing a significant role in Alzheimer's disease research. It exhibits excellent antioxidant properties, metal ion chelation ability, reduces oxidative stress, and demonstrates neuroprotective and anti-neuroinflammatory activities.

Aβ1-42 aggregation inhibitor 1 effectively inhibits acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values of 2.64 μM and 1.29 μM, respectively. At 25 μM, it also reduces self-mediated Aβ1-42 aggregation by 51.29%, showcasing its potential for Alzheimer's disease research [1].

CGP 3466B maleate (Omigapil maleate) is an orally bioavailable GAPDH nitrosylation inhibitor. Omigapil maleate abrogates Aβ1-42-induced tau acetylation, memory impairment, and locomotor dysfunction in mice. Omigapil maleate has the potential for the research of Alzheimer's disease. Omigapil maleate (CGP3446B maleate) is a apoptosis inhibitor. Omigapil maleate can be used for the research of congenital muscular dystrophy (CMD).

Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4(Aftin4) increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4(Aftin4) can thus be used to induce a rapid, acute Alzheimer's disease-like toxicity in the rodent brain.

H3R antagonist 4 (compound 11l) serves as a dual inhibitor of cholinesterases and histamine H3 receptors (H3R), demonstrating IC50 values of 7.04 μM (eeAChE), 9.73 μM (hAChE)(reversible), and 1.09 nM (H3R). It effectively inhibits both self and Cu2+-induced Aβ1-42 aggregation at 95.48% and 88.63%, respectively, and degrades Aβ1-42 protofibrils with 80.16% and 89.30% efficiency under similar conditions. Additionally, H3R antagonist 4 possesses the chelating capability for biometals Cu2+, Zn2+, Al3+, and Fe2+. It significantly reduces tau protein hyperphosphorylation induced by Aβ1-42, inhibits RSL-3 induced apoptosis and ferroptosis in PC12 cells, and shows optimal blood-brain barrier permeability and intestinal absorption characteristics in hCMEC/D3 and hPepT1-MDCK cells, respectively. Moreover, the compound improves learning and memory impairments in an Alzheimer's mouse model induced with scopolamine.

D-688 serves as an inhibitor of Tau and Aβ. It can reverse the cytotoxicity in SH-SY5Y cells induced by Aβ1–42, displaying significant neuroprotective characteristics. Additionally, D-688 enhances the survival rate of transgenic fruit flies expressing the human tau protein isoform (2N4R).

D-687 is an inhibitor of Tau and Aβ. It effectively reverses the cytotoxicity induced by Aβ1–42 in SH-SY5Y cells, demonstrating significant neuroprotective properties.

AChE BChE-IN-23 (Compound 6e) is a dual inhibitor of acetylcholinesterase and butyrylcholinesterase, exhibiting IC50 values of 0.91 μM for AChE, 1.19 μM for eqBChE, and 1.01 μM for hBChE. This compound also demonstrates antioxidant properties and inhibits the aggregation of Aβ1-42 and Tau proteins. Moreover, AChE BChE-IN-23 prevents the activation of microglial cells by inhibiting the release of reactive oxygen species and mitochondrial damage. Additionally, it reduces the levels of the NLRP3 inflammasome in human microglial cells and reverses memory impairment in mice induced by scopolamine.

JNK3inhibitor-9 (Compound 24a) is a potent, selective JNK3 inhibitor capable of crossing the blood-brain barrier (BBB), demonstrating an IC50 value of 12 nM. It effectively inhibits GSK3α β, which is involved in Tau phosphorylation, with IC50 values of 14 nM and 35 nM, respectively. JNK3inhibitor-9 also reduces the phosphorylation of c-Jun and APP and protects neurons from Aβ1-42 toxicity.

hAChE-IN-10 (Compound ET11) is an inhibitor of human acetylcholinesterase (AChE) with an IC50 of 6.34 nM. This compound is capable of scavenging free radicals and exhibits antioxidant activity. Additionally, hAChE-IN-10 demonstrates metal-chelating properties, inhibiting Cu2+-induced Aβ1-42 aggregation, reducing amyloid plaque formation, and offering neuroprotective effects. It also ameliorates cognitive impairment in mice induced by Scopolamine.

AChE-IN-51 (compound 8C) is an orally active, non-competitive inhibitor of AChE and BChE, with IC50 values of 84 nM and 97 nM, respectively. It also inhibits MMP-2 and amyloid β Aβ1-42 aggregation, with IC50 values of 724 nM and 302 nM. Exhibiting low cytotoxicity, AChE-IN-51 is predicted by computational models to penetrate the blood-brain barrier, making it a useful compound for research into diseases such as Alzheimer's disease (AD).

BChE-IN-30 (compound (R)-37a) is a BChE inhibitor with an IC50 of 5 nM, demonstrating anti-inflammatory properties and low toxicity. This compound can alleviate cognitive deficits induced by scopolamine and Aβ1-42 peptide, making it applicable for advanced-stage Alzheimer's disease research.

hAChE/hBACE-1-IN-1 (compounds 5d) is an orally active inhibitor of hAChE that can cross the blood-brain barrier. It effectively inhibits hAChE and hBACE-1, with IC50 values of 0.076 and 0.23 μM, respectively. Additionally, hAChE/hBACE-1-IN-1 prevents Aβ1-42 aggregation and enhances learning and memory in mice. This compound is useful in Alzheimer's disease research.

AChE-IN-62 (Compound 1) is a potent, mixed-type selective inhibitor of acetylcholinesterase (AChE) with an IC50 value of 0.421 μM. It effectively penetrates the blood-brain barrier and offers neuroprotective effects. Additionally, AChE-IN-62 inhibits the aggregation of Aβ1-42 with an IC50 of 44.64 μM. This compound also acts as an effective multi-target-directed ligand (MTDL) and is applicable in Alzheimer's disease research.

Multitarget AD inhibitor-2 (Compound VN-19) is a versatile inhibitor targeting multiple sites, acting on acetylcholinesterase (AChE, IC50 = 0.14 μM), butyrylcholinesterase (BChE, IC50 = 11.6 μM), and monoamine oxidase B (MAO B, IC50 = 0.45 μM). It inhibits amyloid-beta protein Aβ1-42 self-induced aggregation with an inhibition rate of 47.3% at 20 μM and reduces ROS levels in SH-SY5Y cells with an inhibition rate of 80% at 25 μM. Multitarget AD inhibitor-2 can also improve cognitive decline in a scopolamine-induced Alzheimer's zebrafish model.

Ab42-IN-C2 is an Aβ1-42 inhibitor.

Ginsenoside Rg2 (Chikusetsusaponin I) is one of the major active components of ginseng, act as an NF-κB inhibitor.

Potent and selective β-secretase (BACE) inhibitor (IC50 values are 10.2 and 20.3 nM for human BACE2 and BACE1, respectively). Displays >5,000-fold selectivity for BACE over other proteases including cathepsin D, pepsin and renin. Inhibits Aβ1-40 and Aβ1-42 production in cells expressing mutated APP. Reduces hippocampal and cortical Aβ and sAPPβ levels in an Alzheimer's disease mouse model.