aggregates

CGP52411 is an orally active, and ATP-competitive inhibitor of EGFR (IC50: 0.3 μM). CGP52411 blocks the toxic influx of Ca2+ ions into neuronal cells and dramatically inhibits and reverses the formation of β-amyloid Aβ42 fibril aggregates. CGP52411 can be used in studies about Alzheimer's diseases.

Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease

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.

EN6-mediated ATP6V1A modification decouples the v-ATPase from the Rags, leading to inhibition of mTORC1 signaling, increased lysosomal acidification and activation of autophagy. EN6 clears TDP-43 aggregates, a causative agent in frontotemporal dementia, in a lysosome-dependent manner. EN6 is a small-molecule in vivo activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal the vacuolar H+ ATPase (v-ATPase).

ESI1 is a small molecule inhibitor of epigenetic silencing. This compound induces the formation of nuclear aggregates of the key lipid metabolism regulator SREBP1 2, thereby concentrating transcription co-activators to drive lipid cholesterol biosynthesis. Additionally, ESI1 promotes myelin regeneration in demyelination animal models and facilitates de novo myelination on regenerating CNS axons, reversing age-related cognitive decline.

Aβ-IN-10 (Compound Alz-5) is a bifunctional copper chelator and an inhibitor of beta-amyloid (Aβ), interacting with Aβ aggregates to reduce their neurotoxicity. This compound also displays antioxidative properties and exhibits moderate cytotoxicity in SH-SY5Y and HepG2 cells in the presence of CuCl2, with IC50 values of 65.5 and 31.2 μM, respectively. Additionally, Aβ-IN-10 reduces the increase in cell rigidity caused by Aβ.

Biotinylated isoxazole is a biotin-conjugated derivative of isoxazole. It can induce the formation of aggregates associated with RNA granules.

PBA-1105 TFA is an autophagy-targeting chimera (AUTOTAC) that induces p62 self-oligomerization. This compound selectively binds to the exposed hydrophobic regions of misfolded proteins, promoting their degradation through the autophagy (autophagy) pathway. Additionally, PBA-1105 TFA enhances the autophagic flux of Ub-bound aggregates.

EPPS is a rescuer of A aggregation and behavioral deficits. It binds to A aggregates and converts them into monomers.

Cariporide (HOE-642) (HOE-642), an effective NHE1 inhibitor, has inhibitory effects on the degranulation of human platelets, the formation of platelet-leukocyte-aggregates, and the activation of the GPIIb IIIa receptor (PAC-1).

CRANAD-2 is a difluoroboron-derivatized curcumins as near-infrared probe for in vivo detection of amyloid-beta deposits. Upon interacting with Abeta aggregates, CRANAD-2 undergoes a range of changes, which include a 70-fold fluorescence intensity increase, a 90 nm blue shift (from 805 to 715 nm), and a large increase in quantum yield.

AkaLumine (Aka Lumine) is a firefly luciferin analog that is a luciferase substrate that binds to Abeta aggregates and plaques.AkaLumine is used for in vivo optical imaging.

T-808 is a tau tracer which may be used in radiographic labeling of Tau aggregates during Alzheimer's disease.

Tau tracer 2 (Pl-2620) is a specific imaging agent designed to detect and visualize Tau protein aggregates, primarily used for diagnosing neurodegenerative diseases [1].

Setosusin is a meroterpenoid fungal metabolite originally isolated from C. setosus. It reduces neurotoxicity induced by amyloid-β (Aβ) aggregates in PC12 cells (EC50 = 112.6 μM). In vivo, setosusin (30 mg/kg) induces tremors in mice.

Amylin (8-37), human, derived from human Amylin, possesses direct vasodilator effects in isolated mesenteric resistance arteries of rats. Human Amylin is a small pancreatic β-cell hormone that forms aggregates in the absence of insulin and is a key pathological feature of type II diabetes mellitus.

Tat-beclin 1, a peptide derived from the autophagy protein beclin 1, is a powerful inducer of autophagy. It interacts with GAPR-1 (GLIPR2), a negative regulator of autophagy. Tat-beclin 1 effectively reduces polyglutamine expansion protein aggregates and inhibits various pathogens, such as HIV-1, in laboratory experiments. Additionally, it decreases mortality in mice infected with chikungunya (CHIKV) or West Nile virus (WNV).

Tat-beclin 1 acetate is a potent inducer of autophagy and interacts with the negative regulator of autophagy, GAPR-1. Tat-beclin 1 acetate decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1).

Tau tracer 1 is a radiopharmaceutical agent designed specifically for visualizing Tau protein aggregates, commonly associated with neurodegenerative diseases. Its primary application lies in the diagnosis of these conditions.

AChE BChE BACE-1-IN-2 (Compound 4o) is an orally active AChE, BACE-1, and BChE inhibitor with IC50 values of 0.069, 0.097, and 0.127 μM against hAChE, hBACE-1, and hBChE, respectively. It exhibits remarkable antioxidant potential, considerable binding capability towards PAS-AChE, potential disassembly of Aβ aggregates, and neuroprotective activity against Aβ-induced stress with excellent brain permeation [1].

THK-5117 is an arylquinoline derivative with the potential as a PET probe for tau imaging. THK-5117 shows high binding affinity to tau fibrils with a Ki value of 10.5 nM. THK-5117 also shows high binding affinity to tau protein aggregates and tau-rich Alzheimer disease (AD) brain homogenates [1].

SEN177 shows the potential in the research of Huntington's disease that is a potent inhibitor of glutaminyl cyclase (QPCT) with an IC 50 of 0.013μM for glutaminyl-peptide cyclotransferase-like (QPCTL). The Ki value of SEN177 for human glutaminyl cyclase (hQC) is 20 nM. SEN177 significantly reduces the early stages of mutant HTT oligomerisation and reduces the percentage of neurons with Q80 aggregates [1].

THK-5105, an arylquinoline derivative, demonstrates high binding affinity for tau fibrils, protein aggregates, and tau-rich Alzheimer's disease (AD) brain homogenates, indicating its potential as a tau imaging PET (Positron Emission Tomography) probe with the radiolabeled version, 18F-THK-5105 [1].

AChE BChE BACE-1-IN-1 (Compound 4k) is an orally active inhibitor that targets acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), with IC50 values of 0.058 μM, 0.082 μM, and 0.115 μM against hAChE, hBChE, and hBACE-1, respectively. It exhibits significant binding affinity with PAS-AChE, excellent blood-brain barrier permeability, potential disassembly of amyloid-beta (Aβ) aggregates, neuroprotective properties against Aβ-induced stress, and remarkable antioxidant capabilities [1].