cellular amyloid-β

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].

β-Amyloid (25-35) is a fragment of the Alzheimer’s amyloid beta peptide Aβ(25-35), exhibiting neurotoxic effects and commonly used to establish both cellular and animal models 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.

REM127 is a small molecular compound that modulates cellular calcium homeostasis and provides neuroprotection. It efficiently restores the imbalance of calcium homeostasis in cell models caused by the pathological accumulation of tau protein. Furthermore, REM127 can effectively cross the blood-brain barrier and offers therapeutic benefits in animal models of Alzheimer's disease, particularly in ameliorating synaptic and cognitive deficits and slowing the progression of amyloid-beta and tau pathologies. This compound is utilized in the research of neurodegenerative diseases.

4-FPBUA, a semi-synthetic analog of lichen acid, enhances the functionality of cell-based blood-brain barriers (BBB) and increases the transport of β-amyloid (Aβ) in monolayer cells. Additionally, it acts as an inhibitor of mTOR, enhancing cellular autophagy (Autophagy) which can reverse BBB disruption in vivo, making it relevant for research in Alzheimer's disease.

Lupanine ((+)-Lupanine), a naturally occurring quinolizidine alkaloid, potently affinity and activates nicotinic acetylcholine receptor (nAChR) (Ki=500 nM), and shows significant neuroprotection against soluble amyloid β-oligomers (SO-Aβ) toxicity in cellular models in association with the anti-apoptotic PI3K/ Akt/Bcl-2 signaling pathway with anti-Alzheimer's disease potential. Improves glucose homeostasis by affecting KATP channels and enhancing insulin secretion with therapeutic potential for type 2 diabetes.

[D-Ser14]-Humanin is a biologically active peptide in which the Ser14 residue of Humanin is replaced with its D-form. This variant exhibits effective inhibitory activity against the fibrillation of amyloid-β. Compared to its L-form counterpart, [D-Ser14]-Humanin offers enhanced cellular protective activity against age-related cell death induced by amyloid precursor fibrils and oxidative stress. This compound is utilized in research on Alzheimers disease.