amyloid precursor protein

δ-secretase inhibitor 11 is an inhibitor of δ-secretase and can be used as a lead compound for translational development of AD treatment.

β-Amyloid precursor protein (96-110), cyclized (human), a segment of the amyloid precursor protein, serves as a research tool in Alzheimer's disease studies [1].

Beta-Amyloid Protein Precursor 770 (135-155)Aβ Protein Precursor 770 (135-155)

ELN318463 racemate (ELN 318463 racemate) is the racemate of ELN318463 which is an amyloid precursor protein (APP) selective γ-secretase inhibitor.

Atabecestat (JNJ-54861911) is a potent, brain-penetrant, and orally active β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor that achieves robust and high CSF Aβ reduction, is well-tolerated, and displays sustained pharmacokinetic (PK) and pharmacodynamic (PD) characteristics. Atabecestat (JNJ-54861911) has the potential for Alzheimer's Disease treatment[1].

DSS30 is a P25 CDK5 inhibitor.DSS30 acts by inhibiting the phosphorylation of amyloid precursor protein cleaving enzyme 1 (BACEl), which reduces the secretion of β-amyloid (Aβ).DSS30 can be used for the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease.

HEPPS exhibits inhibitory activity against the amyloid-beta precursor protein, reducing Aβ aggregation burden and improving neuronal autophagy flux, thereby alleviating neuronal apoptosis and traumatic brain injury (TBI) in mice. It can be used for research into Alzheimer's disease and neurological disorders.

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.

Anatabine dicitrate, a tobacco alkaloid that can cross the blood-brain barrier, is a potent α4β2 nAChR agonist and inhibits NF-κB activation, thereby reducing amyloid-β (Aβ) production by preventing β-cleavage of the amyloid precursor protein.

BACE1-IN-5 (Compound 15), a potent β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor, demonstrates significant efficacy with an IC50 of 9.1 nM for BACE1 inhibition and an impressive IC50 of 0.82 nM against cellular amyloid-β (Aβ) production. Additionally, it is engineered to enhance hERG inhibition and P-gp efflux, indicating its optimized medicinal chemistry profile [1].

ELN 318463 shows differential inhibition of presenilin (PS1)- and PS2-comprised γ-secretase with EC50s of 12 nM and 656 nM for PS1 and PS2, respectively. ELN 318463 is 51-fold more selective for PS1.ELN 318463 is an amyloid precursor protein (APP) selective γ-secretase inhibitor.

PF-06751979 is an inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) (IC50 of 7.3 nM in BACE1 binding assay).

Umibecestat is an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), with IC50s of 11 nM and 10 nM for human BACE-1 and mouse BACE-1, respectively. Umibecestat can be used for the research of alzheimer's disease.

Begacestat (GSI-953) is a potent and selective gamma-secretase inhibitor (γ-secretase) that inhibits Amyloid-beta production with nanomolar potency, selectively inhibits cleavage of APP in cellular level Notch cleavage assays, reverses situational memory deficits, and can be used to study Alzheimer's disease.

BMS 299897 is a sulfonamide γ-secretase inhibitor with an IC50 of 7 nM for inhibiting Aβ production in HEK293 cells stably overexpressing amyloid precursor protein (APP).

Aβ aggregation-IN-1 (Compound 1b) is an inhibitor of amyloid-beta precursor protein. It suppresses the aggregation and disaggregation of amyloid-beta fibrils with IC50 values of 3.92 and 7.19 M, respectively. Additionally, Aβ aggregation-IN-1 reduces malondialdehyde formation in neuronal cells, increases intracellular levels of reduced glutathione (GSH), and inhibits caspase 3.

Gamma-secretase modulator 6 (Example 50) is a gamma-secretase modulator. It inhibits Aβ42 secretion in HEK cell lines stably expressing APP (Aβ amyloid precursor protein) with a pIC50 of 8.1. This compound is applicable in Alzheimer's disease research.

Leucyl-phenylalanine amide is an intermediate in the synthesis of γ-Secretase Inhibitor, the enzyme complex that catalyzes the cleavage of the amyloid precursor protein (APP) to produce amyloid β-peptide (Aβ) which is the major causative agent in Alzheime

LY3202626, an amyloid precursor protein secretase (BACE protein) inhibitor, is used for the treatment of Alzheimer's disease.

BACE-IN-1 is amyloid precursor protein beta-secretase inhibitor

BACE-IN-1 acetate (BACE-IN-1 acetate (350228-37-4,Free base)) has been used as β-site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) inhibitor in BACE1 inhibitor assay. β-Site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1), an aspartic protease belongs to the protease family of enzymes comprises of six luminal cysteine residues. These residues help in the formation of three intermolecular disulfide bonds and N-linked glycosylation sites.

Usmarapride free base (SUVN-D4010 free base) is a selective and orally active 5-HT4 receptor partial agonist, increasing soluble amyloid precursor protein α levels, useful in Alzheimer's disease research.

16F16 is a protein disulfide isomerase (PDI) inhibitor.1It inhibits PDI reductase activity in an enzyme assay when used at concentrations ranging from 1 to 100 μg/ml.116F16 reduces PC12 cell apoptosis induced by the misfolded huntingtin protein HTTQ103. It suppresses PDI-dependent mitochondrial outer membrane permeabilization (MOMP) in isolated PC12 cell mitochondria. 16F16 (2, 3, 4, and 10 μM) reduces HTTN90Q73mutant huntingtin-induced medium spinal neuron death and MOMP in rat corticostriatal slices. It also reduces pyramidal neuron death induced by amyloid-β precursor protein (APP) in rat corticostriatal slices. 1.Hoffstrom, B.G., Kaplan, A., Letso, R., et al.Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteinsNat. Chem. Biol.6(12)900-906(2010)

Donecopride is a partial agonist of the serotonin (5-HT) receptor subtype 5-HT4E(Ki= 8.5 nM) and an inhibitor of acetylcholinesterase (AChE; IC50= 16 nM).1It is selective for AChE over butyrylcholinesterase (BChE; IC50= 3,530 nM) but does bind to 5-HT2Band sigma-2 (σ2) receptors (Ki= 1.6 nM for both) in a panel of 42 neurotransmitter receptors and transporters. Donecopride induces release of soluble amyloid precursor protein-α (sAPP-α) in COS-7 cells transiently expressing 5-HT4with an EC50value of 11.3 nM. Oral administration of donecopride (1 mg/kg) reduces brain soluble and insoluble amyloid-β (1-42) levels and increases the time spent exploring the novel object in the novel object recognition (NOR) test in the 5XFAD transgenic mouse model of Alzheimer's disease. Donecopride (3 mg/kg, p.o.) prevents a reduction in spontaneous alternation behavior induced by intracerebroventricular administration of soluble Aβ42 (sAβ42) in the Y-maze in mice.2 1.Lecoutey, C., Hedou, D., Freret, T., et al.Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatmentProc. Natl. Acad. Sci. USA111(36)E3825-E3830(2014) 2.Rochais, C., Lecoutey, C., Hamidouche, K., et al.Donecopride, a Swiss army knife with potential against Alzheimer's diseaseBr. J. Pharmacol.177(9)1988-2005(2020)