aβ aggregation-in-1

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.

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.

BuChE-IN-TM-10 (TM-10) is a potent inhibitor of butyrylcholinesterase (BuChE) with an IC50 of 8.9 nM. It effectively inhibits and disaggregates self-induced Aβ aggregation, exhibits significant antioxidant activity, and demonstrates substantial penetration through the blood-brain barrier (BBB), holding promise as a potential treatment for Alzheimer's disease.

Amyloid-β-IN-1 (compound 13), a synthetic peptide featuring the hydrophobic C-terminal segment "VVIA-NH2" and its reversed sequence "AIVV-NH2" derived from Aβ 42, acts as an Aβ inhibitor. It effectively inhibits Aβ aggregation and exhibits neuroprotective effects.

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.

hAChE-IN-8 (Compound S-12) is an orally active and selective inhibitor of hAChE, with an IC50 of 0.486 μM. It also inhibits BACE-1 with an IC50 of 0.542 μM, but shows negligible inhibition of Dyrk1A (IC50>10 μM). This compound reduces Aβ aggregation, exhibits good blood-brain barrier penetration, and is primarily used in Alzheimer's disease research.

BuChE-IN-11 (Compound 3b-1) is a selective inhibitor of BuChE with an IC50 of 0.44 μM for hBuChE. The compound demonstrates high brain-blood barrier permeability and possesses free radical scavenging capabilities, indicating significant antioxidant activity. BuChE-IN-11 interacts with the choline binding site, the acyl binding site, and the peripheral anionic site, showing submicromolar inhibitory activity against BuChE and preventing the self-aggregation of β-amyloid protein (Aβ). This compound holds promise for research in the field of Alzheimer's disease.

SEN-1269 is an amyloid-β (AB) aggregation inhibitor that acts by blocking Aβ(1-42) aggregation and protecting neuronal cell lines exposed to Aβ(1-42), reducing Aβ oligomer-induced LTP and memory deficits in vivo.

1. N-trans-Feruloyltyramine (Feruloyltyramine)(NTF) has hepatoprotective effect. 2. NTF has antioxidative activity against Aβ(1-42)-induced neuronal death. 3. NTF is likely to inhibit COX enzymes, thereby suppressing P-selectin expression on platelets, is a platelet aggregation inhibitor. 4. NTF inhibits melanogenesis in a dose-dependent manner, NTF induces downregulation of tyrosinase resulted in suppression of melanin biosynthesis in murine B16 melanoma cells.

AChE/BuChE-IN-2 (Compound 5f) is an orally active inhibitor of AChE and BuChE with IC50 values of 0.72 μM and 0.16 μM, respectively, and can cross the BBB. AChE/BuChE-IN-2 shows potent inhibition of self-induced β-amyloid (Aβ) aggregation with an IC50 of 62.52 μM and demonstrates non-competitive inhibition with AChE [1].

ChE/Aβ1-42-IN-1 (compound 28) is a potent aggregation inhibitor of ChE and Aβ1-42 with excellent BBB permeability, exhibiting IC50 values of 0.062 μM for AChE, 0.767 μM for BuChE, and 1.227 μM for Aβ1-42 aggregation. ChE/Aβ1-42-IN-1 is a potent multi-targeted anti-Alzheimer's disease agent [1].

HDAC6-IN-6 (compound 6a) is a potent HDAC6 inhibitor with an IC50 value of 0.025 μM that can penetrate the BBB. It exhibits strong inhibitory activity against AChE and Aβ 1-42 self-aggregation with IC50 values of 0.72 and 3.0 μM, respectively. HDAC6-IN-6 also enhances neurite outgrowth without significant neurotoxicity [1].

Aβ-IN-5 (Compound e12) is an orally active inhibitor of Aβ aggregation and also inhibits AChE and BuChE with IC50 values of 21.29 μM and 1.32 μM, respectively. Additionally, Aβ-IN-5 demonstrates significant neuroprotective effects and low neurotoxicity [1].

BuChE-IN-6 (compound 1b) is a highly effective and specific inhibitor of BuChE (butyrylcholinesterase), with IC50 values of 0.46 μM for eqBuChE and 0.51 μM for hBuChE. Additionally, it inhibits the self-aggregation of Aβ 42 [1].

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].

MAO-B-IN-10 (compound 4f) is a highly potent and selective MAO-B (monoamine oxidase-B) inhibitor that effectively penetrates the blood-brain barrier, exhibiting an IC50 of 5.3 μM. It demonstrates the ability to inhibit self-mediated Aβ (amyloid β) aggregation by 58.2% and disaggregate it by 43.3%, holding promise for Alzheimer's disease research [1].

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated inhibitor of HDAC6 (IC50 = 0.025 μM) that inhibits Aβ 1-42 self-aggregation and AChE with IC50 values of 3.0 and 0.72 μM, respectively. Additionally, HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

Antioxidant agent-8, an orally active compound, inhibits Aβ 1-42 deposition by preventing fibril aggregation (IC 50 = 11.15 µM) and aiding in fibril disaggregation (IC 50 = 6.87 µM). It counteracts Cu2+-induced Aβ 1-42 fibril aggregation and disaggregation with lower IC 50 values of 3.69 µM and 3.35 µM, respectively. Additionally, it exhibits antioxidant and anti-inflammatory activities, demonstrates biosafety and blood-brain barrier permeability, and provides a neuroprotective effect.

AChE/BuChE-IN-1, a selective butyrylcholinesterase (BuChE) inhibitor derived from chrysin, exhibits a potent efficacy with an IC50 of 0.48 μM against BuChE and a lesser inhibitory effect on acetylcholinesterase (AChE) with an IC50 of 7.16 μM. It demonstrates significant hydroxyl radical (·OH) scavenging activity, achieving an IC50 of 0.1674 μM, and effectively inhibits reactive oxygen species (ROS) and Aβ 1-42 aggregation, including self-aggregation, copper (Cu 2+)-induced, and AChE-induced aggregation. Characterized by high blood-brain barrier (BBB) permeability, bioavailability, and low cellular toxicity, AChE/BuChE-IN-1 holds promising potential for Alzheimer's disease (AD) research.

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].

MAO-B-IN-21 is an MAO-B inhibitor characterized by superior antioxidant and anti-Aβ aggregation activities, metal-ion chelating capabilities, and mitigation of neuroinflammation (NO, TNF-α). It demonstrates neuroprotective effects with notable BBB permeability and, in an Aβ1-42 induced Alzheimer's disease mouse model, significantly enhances memory and cognitive functions [1].

LPYFD-NH2 TFA, a pentapeptide, inhibits Aβ(1-42) aggregation, indicating its potential utility in Alzheimer's disease research [1].