tau aggregation

Aβ/tau aggregation-IN-4 (Compound D21) is an inhibitor of Aβ/tau aggregation. It promotes the degradation of Aβ40/42 with IC50 values of 2.151 μM for Aβ40 and 3.622 μM for Aβ42. This compound selectively inhibits AChE with an IC50 of 5.56 μM and also inhibits MAO-A and MAO-B with IC50 values of 0.59 μM and 0.09 μM, respectively. Additionally, Aβ/tau aggregation-IN-4 reduces intracellular ROS levels and is used in Alzheimer's disease research.

Aβ/tau aggregation-IN-1 is a potent inhibitor of Aβ 1-42 β-sheet formation and tau aggregation, exhibiting K D values of 160 μM and 337 μM with Aβ 1-42 and tau, respectively. Additionally, Aβ/tau aggregation-IN-1 efficiently penetrates the blood-brain barrier.

Aβ/tau aggregation-IN-3 is a potent inhibitor of amyloid protein aggregation, with an IC50 value of 0.85 µM in an Aβ-Thioflavin T (Aβ-ThT) functional aggregation assay, demonstrating anti-amyloid activity [1].

Tau-aggregation-IN-1 is a dopamine D2 and D3 receptor agonist and an inhibitor of tau441 protein aggregation (IC50: 21 μM).

Tau/Aβ40 aggregation-IN-1 (Compound 20) functions as an inhibitor for tau and Aβ 40 aggregation, exhibiting IC50 values of 1.8 μM and 1.3 μM, respectively [1].

Tau-aggregation-IN-3 (compound 9), a Tau protein aggregation inhibitor (TAI), demonstrates effectiveness in cell-based aggregation inhibition experiments with an EC50 of 4.816 μM. It is applicable in Alzheimer's disease research [1].

Tau Protein Aggregation-IN-1 (Compound 0c) serves as an inhibitor of Tau protein aggregation, applicable in research related to protein folding disorders including Alzheimer's disease, dementia, Parkinson's disease, Huntington's disease, and prion-based spongiform encephalopathies [1].

Tau-aggregation and neuroinflammation-IN-1 is a potent inhibitor of tau protein aggregates, showing significant inhibitory activity against AcPHF6 and full-length tau protein aggregates. It has anti-inflammatory activity, reduces NO release, exhibits low cytotoxicity against LSP-stimulated BV2 cells, and reverses okadaic acid-induced memory impairment in rats.

Aβ-IN-1 TFA inhibits and reverses different types of protein aggregation.

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.

GSK-3β Inhibitor21 (compound 44) is an ATP-competitive inhibitor of GSK-3β with an IC50 value of 6.06 µM, characterized by its ability to inhibit tau phosphorylation and prevent amyloid protein aggregation. This compound is utilized in the research of Alzheimer's 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.

Simufilamum (also known as PTI-125) is an oral small-molecule compound candidate that targets altered conformations of filamin A. It binds and reverts the misfolded filamin A in the brains of Alzheimer's disease patients, thereby slowing the disease's pathological progression. Additionally, PTI-125 reduces tau protein hyperphosphorylation, decreases Aβ42 aggregation and deposition, neurofibrillary tangles, and neuroinflammation. The compound demonstrates concentration-dependent efficacy in vitro, starting at 1 picomolar (pM), in both control groups and post-mortem hippocampal slices from Alzheimer's disease (AD) patients. PTI-125 is the first therapeutic candidate to preferentially bind and reverse pathogenic protein conformations.

tau Protein/α-synuclein-IN-2 (Compound 14T) is a tau and α-synuclein inhibitor capable of crossing the blood-brain barrier. It reduces α-synuclein oligomerization in a dose-dependent manner through a thiourea linker structure. In biosensor cells, tau Protein/α-synuclein-IN-2 prevents tau aggregation seed effects. In the M17D neuroblastoma model, this compound exhibits anti-inclusion effects and reduces Aβ plaque formation. tau Protein/α-synuclein-IN-2 shows potential for Alzheimer's and Parkinson's disease research.

hAChE/hBuChE/GSK-3β-IN-1 (Compound 6c) is a multi-target compound designed for Alzheimer's treatment capable of crossing the blood-brain barrier. It inhibits hAChE with an IC50 of 28.88 nM, hBuChE with an IC50 of 131.90 nM, and GSK-3β with an IC50 of 51.42 nM. Additionally, it acts as an inhibitor of tau protein and Aβ protein aggregation.

GSK-3β inhibitor27 (Compound 1c) is a reversible, competitive inhibitor of GSK-3β with an IC50 value of 2.2 μM. It inhibits tau hyperphosphorylation and reduces Aβ protein aggregation, demonstrating metal chelation and neuroprotective potential. GSK-3β inhibitor27 is promising for research into neurodegenerative diseases, such as Alzheimer's disease.

TAU-IN-4 (compound I1.21) is a potent inhibitor of Tau aggregation, with a KD value of 1.58 μM. It is applicable in Alzheimer's disease research.

MAO-B-IN-31 (Compound 30) is a potent and selective inhibitor of monoamine oxidase B (MAO-B) with an IC50 value of 41 nM. Additionally, MAO-B-IN-31 inhibits the aggregation of α-synuclein (α-syn) and tau proteins, and it also exhibits neuroprotective properties.

GSK-3β inhibitor16 (compound 7c) is a GSK-3β inhibitor with an IC50 value of 4.68 nM. It reduces the aggregation of excessively phosphorylated Tau proteins and shows improvement in scopolamine-induced cognitive impairment in mice.

CHIPOpt is a peptide and an orthosteric inhibitor of the CHIP TPR domain, with a dissociation constant (Kd) of approximately 16 nM. It exhibits anti-aggregation properties and reduces p.tau ubiquitination, while having minimal impact on unmodified tau protein. CHIPOpt is applicable in Alzheimer's disease research.

AChE/BChE-IN-29 is an inhibitor of AChE/BChE. This compound exhibits balanced dual cholinesterase inhibitory activity, with an IC50 value of 2.1 μM against electric eel acetylcholinesterase (eeAChE) and 6.3 μM against horse serum butyrylcholinesterase (eqBChE). In an E. coli cell model, AChE/BChE-IN-29 effectively inhibits the aggregation of amyloid-β (Aβ42) and tau protein. It is a useful agent for Alzheimer's disease (AD) research.

Aha1/Hsp90-IN-2 is a selective inhibitor of the Hsp90/Aha1 interaction, with an IC50 of 1.46 μM. By specifically blocking the binding of Hsp90 to Aha1, Aha1/Hsp90-IN-2 inhibits the activation of Hsp90 ATPase activity mediated by Aha1, thereby reducing tau protein aggregation. This compound can be used for researching neurodegenerative diseases such as Alzheimer's disease.

GSK-3β/G9a-IN-1 (Compound T2) is an orally active, selective inhibitor that penetrates the blood-brain barrier, targeting G9a (substrate-competitive, IC50: 1.1 μM) and GSK-3β (ATP-competitive, IC50: 0.8 μM). It acts as a potent H3K9me2 inhibitor, facilitating chromatin remodeling and reducing tau protein phosphorylation and Aβ aggregation. Additionally, GSK-3β/G9a-IN-1 inhibits the glucocorticoid receptor, androgen receptor, and alpha-2A adrenergic receptor, and upregulates SAGA complex members such as Eny2 and Sgf29. This compound significantly enhances memory, restores social behavior, and increases synaptic complexity in late-onset Alzheimer's disease.

MAO-B-IN-50 (Compound C20) is a selective MAO-B inhibitor with an IC50 value of 0.06 μM. It effectively inhibits the aggregation of Aβ40/42 and Tau proteins, with an overall IC50 of approximately 1 μM. Additionally, MAO-B-IN-50 exhibits potent and selective AChE inhibitory activity (IC50 = 1.78 μM). This compound is useful in Alzheimer's disease research.