aβ1-42

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].

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).

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

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

MAO-B-IN-9 is a monoamine oxidase B MAO-B inhibitor (IC50: 0.18 μM) that crosses the blood-brain barrier with potency, selectivity and time-dependence. MAO-B-IN-9 has neuroprotective effects against Aβ1-42-induced neuronal cell death, which may be related to the anti-aggregation effect of Aβ1-42.

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.

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.

Pep63, a neuroprotective peptide (VFQVRARTVA), enhances synaptic plasticity and memory. It competitively binds with Aβ1-42 oligomers, thereby inhibiting the formation of Aβ fibrils. Pep63 is employed in research focused on Alzheimer's disease (AD).

β-Amyloid (1-43)(human) TFA exhibits greater aggregation tendencies and heightened toxicity compared to Aβ1-42. This compound also associates with sAPPα and sAPPβ and has the potential to serve as an additional biomarker for Alzheimer's disease (AD), complementing existing markers [1].

Aβ-IN-2 is a peptide inhibitor of Aβ1-42. Aβ-IN-2 inhibits the in vitro self-aggregation of Aβ1-42 by delaying the growth phase of the Aβ1-42 index or by reducing the number of protofibrils in the steady state.

AChE-IN-6 is an optimal multifunctional ligand that significantly inhibits AChE activity with IC50 values of 0.20 μM and 37.02 nM for EeAChE and HuAChE, respectively, and has anti-Aβ activity (IC50= 1.92 μM for self-induced Aβ1-42 aggregation, IC50= 1.80 μM for disaggregation of Aβ1-42 pro AChE-IN-6 has shown research potential in Alzheimer's disease.

Neuroinflammatory-IN-2 (compound 7i) is a potent anti-neuroinflammatory agent, capable of acting on MAO-B (IC50: 10.30 μM). Neuroinflammatory-IN-2 inhibits 96.33% of Aβ1-42 aggregation at 25 μM. Neuroinflammatory-IN-2 exhibits neuroprotective activity in H2O2-induced PC-12 cell injury. Neuroinflammatory-IN-2 can be used to study Alzheimer's disease.

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated inhibitor of HDAC6 (IC50 = 0.025 μM) that inhibits Aβ 1-42 self-aggregation and AChE with IC50 values of 3.0 and 0.72 μM, respectively. Additionally, HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

HDAC6-IN-6 (compound 6a) is a potent HDAC6 inhibitor with an IC50 value of 0.025 μM that can penetrate the BBB. It exhibits strong inhibitory activity against AChE and Aβ 1-42 self-aggregation with IC50 values of 0.72 and 3.0 μM, respectively. HDAC6-IN-6 also enhances neurite outgrowth without significant neurotoxicity [1].

K284-6111 is an orally effective inhibitor of the Chitinase 3-like 1 protein (CHI3L1). It functions by reducing the expression of inflammatory proteins such as iNOS, COX-2, GFAP, and Iba-1, and inhibits both β-secretase (β-secretase) and NF-κB, leading to a suppression of Aβ production. Furthermore, K284-6111 improves memory impairment in mice induced by Aβ1–42, making it useful for research in Alzheimers disease.

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.

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].

Ab42-IN-C2 is an Aβ1-42 inhibitor.

Chalcones A-N-5, a trihydroxy chalcone derivative, exhibits no cytotoxicity at concentrations below 100 µM (with IC 50 > 1 mM) and notably enhances cell proliferation. It is particularly effective in encouraging neuronal cell growth within damaged brain tissue and demonstrates an ability to inhibit ferroptosis triggered by RSL or erastin, while also reducing lipid peroxidation levels associated with Aβ1-42 protein aggregation. Given these properties, Chalcones A-N-5 represents a promising molecular framework for further development as a lead compound in in vivo studies aimed at researching Alzheimer's Disease (AD) [1].

BDS-I, a marine toxin derived from Anemonia sulcata, functions as a selective inhibitor of the potassium channel, specifically targeting Kv3.4. It impedes the Aβ1-42-induced augmentation of Kv3.4 activity, caspase-3 activation, and distortion of nuclear morphology in NGF-differentiated PC-12 cells. Moreover, BDS-I effectively counteracts the cell death induced by the Aβ peptide [1].

GSK-3β inhibitor 15 (Compound 54), with an IC50 of 3.4 nM, effectively suppresses Aβ 1-42-induced phosphorylation of GSK-3β and tau protein, as well as LPS-induced iNOS expression, demonstrating neuroprotective properties against Aβ 1-42-induced neurotoxicity and indicating potential utility in Alzheimer's disease (AD) research [1].

Antioxidant agent-8, an orally active compound, inhibits Aβ 1-42 deposition by preventing fibril aggregation (IC 50 = 11.15 µM) and aiding in fibril disaggregation (IC 50 = 6.87 µM). It counteracts Cu2+-induced Aβ 1-42 fibril aggregation and disaggregation with lower IC 50 values of 3.69 µM and 3.35 µM, respectively. Additionally, it exhibits antioxidant and anti-inflammatory activities, demonstrates biosafety and blood-brain barrier permeability, and provides a neuroprotective effect.