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.

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).

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.

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.

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)

Rasagiline-13C3is intended for use as an internal standard for the quantification of rasagiline by GC- or LC-MS. Rasagiline is an inhibitor of monoamine oxidase B (MAO-B; IC50= 4.43 nM for the rat brain enzyme).1It is selective for MAO-B over MAO-A (IC50= 412 nM for the rat brain enzyme). It inhibits serum and NGF withdrawal-induced apoptosis of PC12 cells when used at concentrations ranging from 0.01 to 100 μM.2Rasagiline inhibits rat brain MAO-Bin vivo(ED50= 0.1 mg/kg).1It reduces cerebral edema in a mouse model of traumatic brain injury.2Rasagiline (0.1 mg/kg) reduces cortical and hippocampal levels of full-length and soluble amyloid precursor protein (APP) in rats and mice. It also reduces α-synuclein-induced substantia nigral neuron loss and improves motor dysfunction in a mouse model of Parkinson's disease.3Formulations containing rasagiline have been used in the treatment of Parkinson's disease. 1.Youdim, M.B.H., Gross, A., and Finberg, J.P.Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase BBrit. J. Pharmacol.132(2)500-506(2001) 2.Youdim, M.B.H., and Weinstock, M.Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R) aminoindan-5-YL)-ethyl methyl carbamate]Cell. Mol. Neurobiol.21(6)555-573(2001) 3.Kang, S.S., Ahn, E.H., Zhang, Z., et al.α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's diseaseEMBO J.37(12)e98878(2018)

TML-6, an oral curcumin derivative, demonstrates inhibitory effects on the synthesis of β-amyloid precursor protein and β-amyloid (Aβ). Additionally, TML-6 exhibits upregulation of Apo E, suppression of NF-κB and mTOR, and enhancement of the anti-oxidative Nrf2 gene activity. Considering its diverse pharmacological profile, TML-6 holds promise as a valuable research tool for investigating Alzheimer's disease (AD)[1].