Anatabine dicitrate is a tobacco alkaloid that can cross the blood-brain barrier. It is a potent α4β2 nAChR agonist and inhibits NF-κB activation lower amyloid-β (Aβ) production by preventing the β-cleavage of the amyloidprecursorprotein.
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 amyloidprecursorprotein (APP) selective γ-secretase inhibitor.
Leucyl-phenylalanine amide is an intermediate in the synthesis of γ-Secretase Inhibitor, the enzyme complex that catalyzes the cleavage of the amyloidprecursorprotein (APP) to produce amyloid β-peptide (Aβ) which is the major causative agent in Alzheime
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 precursorprotein (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 amyloidprecursorprotein-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 amyloidprecursorprotein (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-amyloidprecursorprotein 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].