Amyloid-β Inhibitor

AChE/MAO-B-IN-7 (VAV-8) is a blood-brain permeable dual inhibitor of acetylcholinesterase (AchE) and MAO-B agent. AChE/MAO-B-IN-7 can also inhibit Aβ42 aggregation for use in Alzheimer's disease (AD) research.

hAChE-IN-10 (Compound ET11) is the inhibitor for human acetylcholinesterase (AChE) with an IC₅₀ of 6.34 nM. hAChE-IN-10 scavenges free radicals, and exhibits antioxidant activity. hAChE-IN-10 exhibits metal chelating activity, inhibits Cu²⁺-induced Aβ1-42 aggregation, reduces the formation of amyloid plaques, and exhibits neuroprotective activity. hAChE-IN-10 ameliorates the Scopolamine (HY-N0296)-induced cognitive impairment in mouse models.

GL-522 (4-Sulfocalix[8]arene) is a Aβ42 inhibitor. GL-522 bind to Aβ42 through nonspecific and multipoint hydrophobic interactions with a K_d of 276  μM. GL-522 effectively inhibits Aβ42 fibrillation and reduces amyloid cytotoxicity. GL-522 can be used for Alzheimer's disease research.

MNP2 is a NLRP3-ASC interaction inhibitor. MNP2 selectively binds to the PYD domain of ASC (K_a=149 nM) and blocks ASC-PYM binding (K_a=58 nM), thereby inhibiting the interaction between ASC and NLRP3 and suppressing the formation of the NLRP3 inflammasome. MNP2 inhibits IL-1β release and caspase-1 maturation, and reduces the efflux of potassium and chloride ions. MNP2 prevents mitochondrial damage and reactive oxygen species production, and significantly decreases NLRP3 inflammasome formation in neurodegenerative pathologies induced by β-amyloid, Tau protein and α-synuclein. MNP2 is applicable for the research of neurodegenerative diseases.

AChE-IN-62 (Compound 1) is an effective mixed and selective acetylcholinesterase (AChE) inhibitor with an IC₅₀ value of 0.421 μM. AChE-IN-62 exhibits excellent blood-brain barrier permeability and neuroprotective effects. Additionally, AChE-IN-62 can inhibit the aggregation of Aβ_1-42 with an IC₅₀ value of 44.64 μM. AChE-IN-62 is also an effective multi-target-directed ligand (MTDL) that can be utilized in the research of Alzheimer's disease.

AChE-IN-85 (Compound 7k) is an AChE inhibitor with an IC₅₀ of 0.083 μM. AChE-IN-85 can inhibit the release of NO, the production of TNF-α and IL-1β, the levels of LDH and ROS, as well as the aggregation of Aβ42. AChE-IN-85 has anti-inflammatory and neuroprotective effects and can be used in the research of diseases such as Alzheimer's disease.

trans-Sobrerol (NRM-331) is a potent mucofluidifying agent. trans-Sobrerol demonstrates an anti-amnesic effect by enhancing hippocampal cholinergic signaling, alongside exhibiting anti-tau and anti-Aβ synthesis properties. trans-Sobrerol mitigates memory impairment induced by Scopolamine (HY-N0296). trans-Sobrerol can be used in the research of Alzheimer's disease.

AY1511 is an amyloid β (Aβ) aggregation inhibitor with low cytotoxicity.

tau/Aβ40 aggregation-IN-1 (Compound 20) is a tau and Aβ₄₀ aggregation inhibitor with IC₅₀s of 1.8 μM and 1.3 μM, respectively.

6’-Methyl paeonol is a paeonol derivative, which inihibits abnormal depolarizations and reduces the Amyloid β-induced ERK phosphorylation. 6’-Methyl paeonol exhibits alleviating activity against Alzheimer’s Disease.

AChE-IN-51 (compound 8C) is an orally active, non-competitive inhibitor of AChE and BChE (IC₅₀: 84 nM, 97 nM). It also inhibits MMP-2 and amyloid Aβ_1-42 aggregates (IC₅₀: 724 nM, 302 nM). AChE-IN-51 has low cytotoxicity and in silico predicted blood-brain barrier permeability. Can be used for research on diseases such as Alzheimer's disease (AD).

Multitarget AD-IN-3 is a brain-penetrant neuroprotective agent. Multitarget AD-IN-3 can selectively inhibit MAO-B with an IC₅₀ of 4.42 μM and a SI of 18.12. Multitarget AD-IN-3 can eliminate ROS. Multitarget AD-IN-3 Multitarget AD-IN-3 can inhibit Aβ_1-42 self-aggregation and can reverse Aβ_1-42-induced mitochondrial membrane depolarization and inhibit apoptosis. Multitarget AD-IN-3 can be used for the research of neurological disease, such as Alzheimer’s disease.

MAO-B-IN-50 (Compound C20) is a selective MAO-B inhibitor with an IC₅₀ value of 0.06 μM. MAO-B-IN-50 shows good inhibitory effects on the aggregation of Aβ40/42 and Tau proteins, with overall IC₅₀ values around 1 μM. MAO-B-IN-50 exhibits potent and selective AChE inhibition (IC₅₀ = 1.78 μM). MAO-B-IN-50 can be used in the research of Alzheimer's disease.

NB-533 is an orally active and brain-penetrant BACE-1 inhibitor with a human IC₅₀ of 0.002 μM. NB-533 also inhibits human cathepsin D with an IC₅₀ of 0.001 μM. NB-533 inhibits amyloidogenic amyloid precursor protein (APP) processing and reduces Aβ₄₀ release. NB-533 reduces brain levels of APP metabolite C99 and Aβ₄₀ in transgenic mice. NB-533 can be used for the research of Alzheimer’s disease.

BChE-IN-49 is an orally active BChE inhibitor with IC₅₀ values of 0.73 μM and 6.43 μM against BChE and AChE, respectively. BChE-IN-49 reduces AChE levels to inhibit the degradation of acetylcholine. By inhibiting GSK-3β, BChE-IN-49 potently activates the Wnt/β-catenin signaling pathway, exerting potent anti-Aβ, antioxidant, anti-neuroinflammatory and anti-apoptotic effects. BChE-IN-49 can be used in research related to Alzheimer's disease.

Aβ-IN-4 (compound 12) is a potent amyloid β (Aβ) inhibitor. Aβ-IN-4 inhibits Aβ42 aggregation. However, Aβ-IN-4 can not alleviate the neurotoxicity of Aβ42 in SH-SY5Y cells. Aβ-IN-4 can not change the aggregation state of Aβ42 into a nontoxic one.

AChE-IN-12 is a potent and blood-brain barrier (BBB) penetrant acetylcholinesterase (AChE) with IC₅₀s of 0.41 μM and 1.88 μM for rat AChE and electric eel AChE. AChE-IN-12 is also a good antioxidant (ORAC = 3.3 eq), selective metal chelator and huMAO-B inhibitor (IC₅₀ = 8.8 μM). AChE-IN-12 has remarkable inhibition of self- and Cu²⁺-induced Aβ_1-42 aggregation, as well as exhibits a good neuroprotective effect. AChE-IN-12 can be used for researching Alzheimer’s disease.

Lycoramine is a blood-brain barrier-penetrating Acetylcholinesterase inhibitor and Galanthamine (HY-76299) derivative. Lycoramine induces Amyloid-beta plaque clearance. Lycoramine induces reversal of cognitive decline and memory improvement. Lycoramine can be used for research on Alzheimer's disease and myasthenia gravis.

AChE/BuChE-IN-3 is a potent and blood-brain barrier (BBB) penetrant AChE and BuChE dual inhibitor with IC₅₀s of 0.65 μM and 5.77 μM for AChE and BuChE. AChE/BuChE-IN-3 also inhibits Aβ_1-42 aggregation. AChE/BuChE-IN-3 has effectively neuroprotective activities and nearly no toxicity on SH-SY5Y cells. AChE/BuChE-IN-3 can be used for researching Alzheimer's disease.

JNK3/Wnt/β-catenin modulator-1 is a brain-penetrant JNK3 inhibitor and Wnt/β-catenin activator. JNK3/Wnt/β-catenin modulator-1 decreases Aβ_1-42 production and reduced ROS generation. JNK3/Wnt/β-catenin modulator-1 inhibits the activation of JNK and Puma, promotes Beclin-1 expression, reduces GSK-3β and BACE1 expression and activates Wnt/β-catenin signaling. JNK3/Wnt/β-catenin modulator-1 improves cognitive and memory performance, attenuates histopathological brain damage, preserves structure of hippocampal pyramidal cells and cerebral cortical neurons. JNK3/Wnt/β-catenin modulator-1 can be used for the research of Alzheimer's disease.