Amyloid-β Inhibitor

TFEB activator 2 is an orally active compound that can cross the blood-brain barrier. TFEB activator 2 can bind to the dopamine transporter (DAT). TFEB activator 2 promotes TFEB nuclear translocation and lysosome biogenesis by targeting the DAT-CDK9-TFEB pathway. TFEB activator 2 has neuroprotective activity and can be used in the research of Alzheimer's disease and other diseases.

SEN177 is an orally effect glutamine cyclase (QC) inhibitor. The K_i of SEN177 for human glutamine cyclase (hQC) is 20 nM, and the IC₅₀ is 13 nM. SEN177 interferes with the interaction between CD47 and SIRRPα, and has anti-tumor activity. SEN177 reduces aggregation and apoptosis caused by HTT mutation in Huntington model, and can be used in the study of neurodegenerative diseases.

Benzenesulphonamide (Compound 1) is a carbonic anhydrase inhibitor. Benzenesulphonamide exhibits CA II inhibitory activity. Benzenesulphonamide reduces ROS and improves the gene expression of amyloid-β40 and 42. Benzenesulphonamide is beneficial for Alzheimer's disease. Benzenesulphonamide derivatives have anticancer, anti-inflammatory, and anticonvulsant activities. Benzenesulphonamide can be used in the research of Alzheimer's disease, epilepsy, inflammatory diseases, leukemia, melanoma, lung cancer, and colon cancer.

Onjisaponin B is an orally active natural product derived from Polygala tenuifolia. Onjisaponin B inhibits NF-κB p65. Onjisaponin B enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin. Onjisaponin B reduces β-amyloid (Aβ) production. Onjisaponin B reduces radiation-induced cell apoptosis. Onjisaponin B has anti-oxidant and anti-inflammatory activities. Onjisaponin B can be used for neurological disease and radiation injury study, and its metabolite tenuifolin (TF) can enter the brain through the BBB.

Fmoc-His (3-Me)-OH is a histidine derivative with a methylated imidazole group. Fmoc-His (3-Me)-OH can be used for the synthesis of the chemically modified tripeptide His (3-methyl)-Arg-Trp (H (3-Me)-RW). Fmoc-His (3-Me)-OH serves as a resin in Fmoc solid-phase synthesis for the generation of the His-(3-Me)-Gly-Lys peptide. Fmoc-His (3-Me)-OH is a building block for the synthesis of NAHIS02-(p-Met). Fmoc-His (3-Me)-OH can be applied in research related to Alzheimer's disease.

Silybin B (Silibinin B) is an orally active amyloid-β aggregation inhibitor and ATR pathway activator that can cross the blood-brain barrier. Silybin B inhibits Aβ fibril formation and promotes amorphous aggregate formation, while activating the ATR-mediated DNA damage repair pathway and inhibiting JNK/p38 MAPK signaling. Silybin B can reduce Cisplatin (HY-17394)-induced neuronal DNA damage and apoptosis. Silybin B has anti-oxidative stress, cell cycle regulation and neuroprotective activities. Silybin B is mainly used in the study of Alzheimer's disease and Cisplatin chemotherapy-related neurotoxicity.

Enrupatinib (EI‐1071) is a potent, orally active, CNS-penetrant and selective CSF1R inhibitor. Enrupatinib inhibits macrophage proliferation and osteoclast differentiation in vitro. Enrupatinib preserves microglia distal to Aβ plaques. Enrupatinib mitigates Alzheimer's disease (AD)-related pathologies by reducing neuroinflammation, preserving neuronal integrity, lowering disease-associated microglia gene expression, and enhancing cognitive function in 5xFAD and J20 mouse models. Enrupatinib reduces tumor-associated macrophage infiltration and enhances antitumor activity of anti-PD-1 antibody in murine colorectal cancer and breast cancer models. Enrupatinib can be used for the research of AD, colorectal cancer, and breast cancer.

Cu(II)GTSM, a cell-permeable Cu-complex, significantly inhibits GSK3β. Cu(II)GTSM inhibits Amyloid-β oligomers (AβOs) and decreases tau phosphorylation. Cu(II)GTSM also decreases the abundance of Amyloid-β trimers. Cu(II)GTSM is a potential anticancer and antimicrobial agent.

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

Pterosin B is an orally active indanone. Pterosin B can be obtained from Pteridium aquilinum. Pterosin B is a Sik3 signaling inhibitor. Pterosin B inhibits Klf5 expression and reduces β-amyloid deposition. Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice. Pterosin B inhibits cardiomyocyte hypertrophy, improves cognitive impairment, and lowers blood glucose. Pterosin B can be used in research on arthritis, Alzheimer's disease, pathological cardiac hypertrophy and diabetes.

Biotinoyl tripeptide-1 (Biotinyl-GHK) is a biotinylating reagent linked to a GHK (glycyl-L-histidyl-L-lysine) tripeptide. Biotin tripeptide-1 is a bioactive peptide with hair care (improves the appearance and feel of hair) and hair growth effects. Biotinoyl tripeptide-1 has a certain affinity for streptavidin. Biotinoyl tripeptide-1 inhibits the production of ROS and has antioxidant effects. Biotinoyl tripeptide-1 reduces the production of carbonylated amyloid-β (Aβ) and inhibits Aβ aggregation. Biotinoyl tripeptide-1 can be used in the study of neurodegenerative diseases.

Cannflavin A can be isolated from Cannabis sativa L.. Cannflavin A has anti-cancer, neuroprotective and anti-inflammatory activity. Cannflavin A inhibits Aβ_1-42 aggregation. Cannflavin A also inhibits kynurenine-3-monooxygenase (KMO) (IC₅₀ = 29.4 μM). Cannflavin A activates apoptosis via caspase-3 cleavage. Cannflavin A exerts anti-inflammatory effects by inhibiting pro-inflammatory enzymes, including prostaglandin E2 and cytochrome c oxidases I and II in PC12 cell line.

ARN2966 is a potent, orally active and cross the blood-brain barrier amyloid precursor protein (APP) translation modulator.

(E/Z)-Sulindac sulfide is a potent γ-secretase modulator (GSM). (E/Z)-Sulindac sulfide selectively reduces Aβ42 production in favor of shorter Aβ species. (E/Z)-Sulindac sulfide can be used for researching Alzheimer’s disease.

4-Hydroxyindole is a type of hydroxyindole in which the 1H-indole at position 4 is substituted by a hydroxyl group. 4-Hydroxyindole serves as an important raw material or intermediate in the synthesis of pharmaceutical products and industrial polymers. 4-Hydroxyindole inhibits amyloid fibrillization and induces liver function impairment, thyroid abnormalities, and blood glucose fluctuations in mice. 4-Hydroxyindole holds potential for research in neurodegenerative diseases and metabolic disorders.

Ganglioside GQ1b (​Tetrasialoganglioside GQ1b) (bovine) sodium is a central and peripheral nervous system ganglioside and an immunostimulator. Ganglioside GQ1b (bovine) sodium modulates NMDA receptor signaling via ERK1/2, PKA, CREB, NR2A, NR2B, and GSK3β, and increases BDNF expression. Ganglioside GQ1b (bovine) sodium reduces Aβ pathology, tau phosphorylation, and APP levels. Ganglioside GQ1b (bovine) sodium can be used for the research of Alzheimer’s disease.

NB-360 is a potent, brain penetrable and orally active β‐secretase 1/2 (BACE1/BACE2) dual inhibitor with IC₅₀ values of 5 and 6 nM. NB-360 can inhibit amyloid-β protein accumulation. NB-360 can be used for the researches of inflammation and neurological disease, such as Alzheimer's disease.

Ponezumab (PF-04360365; RN 1219) is a humanized anti-amyloid-β (Amyloid-β) IgG2 monoclonal antibody. Ponezumab reduces Aβ levels in the central nervous system and improves the performance of mice in various learning and memory models. Ponezumab is applicable to the research of Alzheimer's disease.

IXA62 is an orally active and selective IRE1/XBP1s activator (EC₅₀ = 0.31 μM) that reduces Aβ secretion. IXA62 enhances glucose-stimulated insulin secretion from rat insulinoma cells.

ONC-841 is a blood-brain barrier-permeable, humanized monoclonal antibody targeting SIGLEC10. As an immune checkpoint inhibitor, ONC-841 restores the functions of immune effector cells such as T cells and enhances anti-tumor immune responses by blocking inhibitory signals mediated by SIGLEC10. ONC-841 restores the phagocytic and migratory activities of microglia, and promotes the phagocytosis of Amyloid-β and Tau protein aggregates by microglia. ONC-841 is applicable to research related to solid tumors and Alzheimer's disease.