Amyloid-β Inhibitor

gamma-Secretase Modulators (Amyloid-β production inhibitor) is a Amyloid-β production inhibitor.

Garcinoic acid is an orally active anti-inflammatory agent that crosses the blood-brain barrier. Garcinoic acid also enhances efferocytosis and enzyme/receptor regulation, and selectively inhibits human COX-2, porcine α-amylase, Saccharomyces cerevisiae α-glucosidase and human DNA polymerase β (IC₅₀=11 μM), as well as activates human PXR. Garcinoic acid enhances macrophage efferocytosis via receptors such as MerTK and LRP-1, and promotes the production of pro-resolving lipid mediators. Garcinoic acid inhibits NF-κB activation and pro-inflammatory cytokine secretion, interferes with Aβ aggregation, downregulates NLRP3 inflammasome activity, and binds to targets including CD44 and EGFR to inhibit leukemia cell proliferation. The pharmacological activities of Garcinoic acid, such as antioxidant, anti-inflammatory and lipid metabolism-regulating effects, are widely used in studies related to various diseases including atherosclerosis, Alzheimer's disease, type 2 diabetes, inflammatory bowel disease and viral pneumonia.

Methyl tridecanoate is a fatty acid methyl ester. Methyl tridecanoate exhibits an IC₅₀ of 3.26 μM and a K_i of 2.30 μM against AsOBP21f in Anopheles sinensis. Methyl tridecanoate induces electroantennographic responses in female Anopheles sinensis. Methyl tridecanoate shows a dose-dependent attractive effect on Anopheles sinensis. Methyl tridecanoate weakly inhibits β-amyloid aggregation and AChE activity. Methyl tridecanoate can be used in the research of malaria and Alzheimer's disease.

Beauveriolide I is an ACAT/SOAT inhibitor. Beauveriolide I selectively inhibits macrophage cholesteryl ester synthesis, blocks cholesteryl ester recycling, reduces cholesterol concentration, lipid droplet accumulation, and post-lysosomal cholesterol metabolism, and promotes the degradation of cholesteryl esters preferentially over triglycerides. Beauveriolide I reduces amyloid β peptide secretion. Beauveriolide I exhibits insecticidal and weak antibacterial activities. Beauveriolide I can be used in research on atherosclerosis, Alzheimer's disease, and cancer.

Cromolyn-d₅ (Cromoglycate-d₅) is the deuterium labeled Cromolyn (HY-B1619). Cromolyn (Cromoglycate) is an orally active GSK-3β inhibitor with an IC₅₀ of 2.0 μM. Cromolyn is also a mast cell stabilizer that can inhibit the release of mediators from mast cells, regulate reflex bronchoconstriction, and reduce non-specific bronchial hyperreactivity, and Cromolyn can be used in the research of bronchial asthma. In addition, Cromolyn has multiple activities such as anti-inflammatory, anti-allergic, anti-histamine, anti-cancer, and neuroprotective effects.

Mivelsiran sodium scrambled negative control is the sequence scrambled negative control of Mivelsiran sodium.

HDAC6-IN-5 (compound 11b) is a potent and BBB-penetrated HDAC6 inhibitor, with an IC₅₀ of 0.025 μM. HDAC6-IN-5 exhibits strong inhibitory activity against Aβ_1-42 self-aggregation and AChE, with IC₅₀ values of 3.0 and 0.72 μM. HDAC6-IN-5 can enhance neurite outgrowth without significant neurotoxicity.

FAM labled Mivelsiran (ALN-APP) sodiumis a FAM labled Mivelsiran sodium. Mivelsiran sodium is an siRNA targeting the β-amyloid precursor protein (APP). Mivelsiran sodium induces sequence-specific degradation of APP mRNA via RNA interference, thereby reducing the levels of APP protein and downstream amyloid cleavage products. Mivelsiran sodium reduces β-amyloid protein levels in the brain, alleviates neuroinflammation, and attenuates microglial proliferation. Mivelsiran sodium can be used for research on early-onset Alzheimer's disease.

Cy3 labled Mivelsiran (ALN-APP) sodium is a Cy3 labled Mivelsiran sodium. Mivelsiran sodium is an siRNA targeting the β-amyloid precursor protein (APP). Mivelsiran sodium induces sequence-specific degradation of APP mRNA via RNA interference, thereby reducing the levels of APP protein and downstream amyloid cleavage products. Mivelsiran sodium reduces β-amyloid protein levels in the brain, alleviates neuroinflammation, and attenuates microglial proliferation. Mivelsiran sodium can be used for research on early-onset Alzheimer's disease.

Simufilam dihydrochloride (PTI-125 dihydrochloride) is an orally active FLNA modulator. Simufilam dihydrochloride restores NMDAR signaling and Arc expression. Simufilam dihydrochloride inhibits overactive mTOR signaling by restoring the normal conformation of FLNA, improves insulin sensitivity, reduces Aβ₄₂-induced neuroinflammation and tau protein hyperphosphorylation. Simufilam dihydrochloride can be used for research of Alzheimer's disease.

Glutaminyl Cyclase Inhibitor 3 (compound 212 ), a designed anti-Alzheimer’s compound, is a potent human Glutaminyl Cyclase (GC) inhibitor, with an IC₅₀ of 4.5 nM. Glutaminyl Cyclase-IN-1 (compound 212) significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions.

HDAC6-IN-6 (compound 6a) is a potent and BBB-penetrated HDAC6 inhibitor, with an IC₅₀ of 0.025 μM. HDAC6-IN-6 exhibits strong inhibitory activity against Aβ_1-42 self-aggregation and AChE, with IC₅₀ values of 3.0 and 0.72 μM. HDAC6-IN-6 can enhance neurite outgrowth without significant neurotoxicity.

2-Hydroxy-5-(phenyldiazenyl)benzoic acid-d₅ is the deuterium labeled 2-Hydroxy-5-(phenyldiazenyl)benzoic acid.

Antioxidant agent-2 (comp 3c), an BBB-penetrated antioxidant agent and a selective metal ions chelator, presents good neuroprotective effect and hepatoprotective effect for the study of Alzheimer’s disease.

Multitarget AD-IN-7 is an orally active multi-target anti-AD compound. Multitarget AD-IN-7 exhibits inhibitory activity against GSK-3β and GSK-3α (IC₅₀ = 0.66, 0.83 nM). Multitarget AD-IN-7 upregulates the expression of p-GSK-3β-Ser9, inhibits the phosphorylation of tau-Ser396, targets Aβ_1-42, chelates pathogenic metal ions, scavenges ABTS•+, upregulates the expression of β-catenin and neurogenesis biomarkers, and promotes neurite outgrowth. Multitarget AD-IN-7 improves motor ability in Alzheimer's disease zebrafish. Multitarget AD-IN-7 is applicable to research related to Alzheimer's disease.

TT-1 is an acetylcholinesterase inhibitor (human IC₅₀ = 18.6 μM) and an amyloid β (1-42) aggregation inhibitor with antioxidant capacity, and it exerts antitumor effects by downregulating ADAM10 expression, upregulating MICA, and activating the intrinsic mitochondrial apoptosis pathway. TT-1 can be used for research on Alzheimer's disease, liver cancer, and epilepsy.

Aβ1–42 aggregation inhibitor 2 (compound 7c) is a potent inhibitor of Aβ1-42 aggregation that plays an important role in Alzheimer's disease research. Aβ1–42 aggregation inhibitor 2 displays excellent antioxidant, metal ions chelating, oxidative stress alleviation, neuroprotective and anti-neuroinflammatory activities.

Aβ aggregation-IN-6 is an Aβ aggregation inhibitor with ~60-70% inhibition of Aβ_17-40 aggregation. Aβ aggregation-IN-6 stabilizes Aβ dimer assembly, binds to Aβ steric-zipper assembly. Aβ aggregation-IN-6 can be used for the research of alzheimer's disease.

ChE/GSK-3β-IN-1 (compound 18o) is a potent dual ChE/GSK-3β inhibitor. ChE/GSK-3β-IN-1 exhibits dual inhibition of AChE (IC₅₀ = 1.7 μM), butyrylcholinesterase (BChE) (IC₅₀ = 5.3 μM), and GSK-3β (IC₅₀ = 5.7 μM). ChE/GSK-3β-IN-1 inhibits Aβ1-42 self-aggregation. ChE/GSK-3β-IN-1 can be used for Alzheimer’s disease (AD) research.

Lycoramine hydrobromide is a blood-brain barrier-penetrating Acetylcholinesterase inhibitor and Galanthamine (HY-76299) derivative. Lycoramine hydrobromide induces Amyloid-beta plaque clearance. Lycoramine hydrobromide induces reversal of cognitive decline and memory improvement. Lycoramine hydrobromide can be used for research on Alzheimer's disease and myasthenia gravis.