aβ/tau aggregation-in-1

Aβ tau aggregation-IN-1 is a potent inhibitor of Aβ 1-42 β-sheet formation and tau aggregation, exhibiting K D values of 160 μM and 337 μM with Aβ 1-42 and tau, respectively. Additionally, Aβ tau aggregation-IN-1 efficiently penetrates the blood-brain barrier.

Aβ-IN-1 TFA inhibits and reverses different types of protein aggregation.

hAChE hBuChE GSK-3β-IN-1 (Compound 6c) is a multi-target compound designed for Alzheimer's treatment capable of crossing the blood-brain barrier. It inhibits hAChE with an IC50 of 28.88 nM, hBuChE with an IC50 of 131.90 nM, and GSK-3β with an IC50 of 51.42 nM. Additionally, it acts as an inhibitor of tau protein and Aβ protein aggregation.

BuChE-IN-5 (compound 25b) is a highly potent BuChE inhibitor with an IC50 value of 1.94 μM, effectively inhibiting Aβ and tau protein aggregation in Escherichia coli, and demonstrating significant free radical scavenging and antioxidant activity, making it a valuable tool for Alzheimer's disease research [1].

Tau Aβ40 aggregation-IN-1 (Compound 20) functions as an inhibitor for tau and Aβ 40 aggregation, exhibiting IC50 values of 1.8 μM and 1.3 μM, respectively [1].

hBChE-IN-1 (compound 4), a quinolizidinyl derivative, effectively inhibits human Butyrylcholinesterase (hBChE) with an IC50 value of 7 nM, demonstrating high selectivity against human Acetylcholinesterase (hAChE). It also inhibits tau and Aβ 40 protein aggregation, with IC50 values of 20 and 4.3 μM, respectively, making it valuable for Alzheimer's disease research [1].

Aβ tau aggregation-IN-3 is a potent inhibitor of amyloid protein aggregation, with an IC50 value of 0.85 µM in an Aβ-Thioflavin T (Aβ-ThT) functional aggregation assay, demonstrating anti-amyloid activity [1].

hAChE-IN-5 (compound 49) is a dual inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBuChE), showing IC50 values of 0.17 μM for both enzymes. It also potently inhibits glycogen synthase kinase 3 beta (GSK3β) with an IC50 of 0.21 μM. Furthermore, it effectively inhibits tau protein and Aβ1-42 peptide self-aggregation, and can bind the peripheral anionic site (PAS) to prevent amyloid-beta (Aβ)-induced neurotoxicity. hAChE-IN-5's ability to cross the blood-brain barrier (BBB) supports its potential in developing multitargeted anti-Alzheimer's agents [1].