tau aggregation

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.

Methylene Blue trihydrate (Basic blue 9) is a compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene Blue trihydrate is used as a bacteriologic stain and as an indicator. It inhibits soluble guanylyl cyclase and has been used to treat cyanide poisoning and to lower levels of methemoglobin. It also inhibits tau filament formation (IC50: 1.9μM).

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

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 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-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].

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.

NQTrp is an inhibitor of the aggregation of the tau protein with generic anti-amyloidogenic effects.

Highly neurotoxic cell-permeable analog of PHF6. Induces aggregation of Tau peptides.

Multitarget AD inhibitor-1 is a reversible and selective inhibitor of butyrylcholinesterase (BuChE) with IC50 values of 7.22 μM for human BuChE (hBuChE) and 1.55 μM for equine serum BuChE (eqBuChE). It also exhibits inhibitory activity towards β-secretase (IC50 41.60 μM), amyloid β aggregation (IC50 3.09 μM), and tau aggregation. As a diphenylpropylamine derivative, Multitarget AD inhibitor-1 is promising for research into multifunctional, disease-modifying treatments for Alzheimer's disease.

PE859 is a potent inhibitor of the aggregation of both tau and Aβ.

BSc3094 is a potent Tau aggregation inhibitor that demonstrates the potential for Alzheimer's disease (AD) research.

BuChE-IN-5 (compound 25b) is a highly potent BuChE inhibitor with an IC50 value of 1.94 μM, effectively inhibiting Aβ and tau protein aggregation in Escherichia coli, and demonstrating significant free radical scavenging and antioxidant activity, making it a valuable tool for Alzheimer's disease research [1].

Aha1 Hsp90-IN-1 (Compound 17) is an inhibitor of the Aha1 Hsp90 complex, effectively disrupting their interaction (IC50: 3.32 μM) and inhibiting tau protein aggregation.

Dyrk1A-IN-1 is a triple inhibitor of Dyrk1A kinase activity, tau aggregation, and α-syn oligomers, with an IC50 value of 119 nM for Dyrk1A kinase.

AChE-IN-10 (Compound 24r) is a potent inhibitor of AChE with an IC50 value of 2.4 nM. It decreases amyloid aggregation in the presence of AChE, reduces tau phosphorylation of S396 residues, rescues neuronal morphology, and increases cell viability, thereby providing neuroprotection.