Amyloid-β Inhibitor

BChE-IN-41 is a highly selective Butyrylcholinesterase (BChE) inhibitor (IC₅₀ =12 nM, K_i = 6.6 nM). BChE-IN-41 has high brain penetration with a brain-to-plasma ratio of 9.0. BChE-IN-41 has pro-cognitive effects on mice with AD-like symptoms induced by Scopolamine (HY-N0296) and Aβ_1-42.

Antioxidant agent-8 is an orally active inhibitor of Aβ_1-42 deposition. Antioxidant agent-8 inhibits fibril aggregation (IC₅₀=11.15 µM) and promotes fibril disaggregation (IC₅₀=6.87 µM). Antioxidant agent-8 also inhibits Cu²⁺-induced Aβ_1-42 fibril aggregation (IC₅₀=3.69 µM) and promotes Cu²⁺-induced Aβ_1-42 fibril disaggregation (IC₅₀=3.35 µM). Antioxidant agent-8 has antioxidant activity, anti-inflammatory activity, biosafety, blood-brain barrier permeability and neuroprotective effect.

Junicedric acid is a diterpenoid compound that can be isolated from the resin of the Araucaria araucana tree. Junicedric acid exerts neuroprotective activity by increasing intracellular calcium levels in hippocampal neurons, activating PKC and calcium/calmodulin-dependent protein kinase (CaMKII), and preventing Amyloid-β oligomer-induced synaptic protein loss, apoptosis, and long-term potentiation (LTP) inhibition. Junicedric acid can be used in the study of the pathological mechanisms of neurodegenerative diseases such as Alzheimer's disease.

AChE/MAO-IN-1 (Compound D28) is a potent AChE, MAO-A and MAO-B inhibitor with IC₅₀s of 0.0248, 0.0409 and 0.1108 μM against human AChE, MAO-B and MAO-A, respectively.

Dyclonine (Dyclocaine) is an orally active, blood-brain barrier-permeable piperidine phenylacetone small molecule commonly used as a local anesthetic. Dyclonine acts as a highly selective allosteric antagonist of TRPV3; it also reversibly inhibits G9a, ALDH2 and ALDH3A1, non-competitively blocks AChE. Dyclonine activates the Nrf2/ARE pathway, relieves the epigenetic silencing of FXN, blocks Aβ42 aggregation, and promotes remyelination and reparative polarization of microglia. Dyclonine alleviates pruritus via TRPV3 inhibition; it is used in studies of neurodegenerative disease models based on its AChE inhibitory, antioxidant and remyelinating effects; it sensitizes drug-resistant tumors through ALDH inhibition, and combined use with protease inhibitors induces more tumor cell apoptosis; it inhibits Candida albicans in vitro. Dyclonine can be used for research on multiple diseases including neurodegenerative diseases, cancer and pruritic dermatitis.

AChE-IN-94 is an orally active and blood-brain barrier penetrable AChE inhibitor with an IC₅₀ of 0.40 μM and K_i of 0.28 μM. AChE-IN-94 prevents self-induced and AChE-mediated Aβ_1-42 aggregation. AChE-IN-94 alleviates cognitive/memory deficits in Scopolamine (HY-N0296)-induced amnesic model. AChE-IN-94 can be used for the study of Alzheimer's disease (AD).

AChE/Aβ-IN-1 (compound 32) is a potent and orally active inhibitor of acetylcholinesterase (AChE) with an IC₅₀ of 86 nM, as well as an antagonist of NMDA receptor (GluN1-1b/GluN2B subunit combination) with IC₅₀ of 3.876 μM. AChE/Aβ-IN-1 also inhibits Aβ aggregation and shows good blood-brain barrier permeability and neuroprotection. AChE/Aβ-IN-1 improves cognitive and spatial memory impairment in rats model.

2,2′,4,4′-Tetrahydroxychalcone (Compound 18) is a selective and potent BACE1 inhibitor with an IC₅₀ of 0.62 μM. 2,2′,4,4′-Tetrahydroxychalcone is a derivative of Isoliquiritigenin (HY-N0102) found in Glycyrrhiza uralensis. 2,2′,4,4′-Tetrahydroxychalcone can block the β-cutting step of amyloid precursor protein (APP), thereby reducing the production of β-amyloid (Aβ) peptide. 2,2′,4,4′-Tetrahydroxychalcone can be used for research of Alzheimer’s disease.

Crocetin monomethyl ester (Standard) is the analytical standard of Crocetin monomethyl ester. This product is intended for research and analytical applications. Crocetin monomethyl ester, isolated from Crocus sativus, possesses anti-inflammatory, neuroprotective and antioxidant activity. Crocetin monomethyl ester promotes clearance of amyloid-β by inducing autophagy via the STK11/LKB1-mediated AMPK pathway.

hAChE/Aβ1-42-IN-1 (Compound 16) is a potent inhibitor of hAChE and Aβ1-42 aggregation. hAChE/Aβ1-42-IN-1 shows acceptable relative safety upon hepG2 cell line and excellent BBB penetration with wide safety margin. hAChE/Aβ1-42-IN-1 has the potential for the research of Alzheimer disease (AD).

Protriptyline is a potent tricyclic antidepressant (TCA). Protriptyline inhibits AChE activity with an IC₅₀ value of 0.06 mM and inhibits Aβ self-assembly. Protriptyline can be used for the study of depression and Alzheimers disease.

AChE/Aβ-IN-3 (compound AM5) is a dual inhibitor of AChE and Amyloid-β aggregation with IC_50<.sub> values of 1.29 and 4.93 μM, respectively. AChE/Aβ-IN-3 has antioxidant properties that scavenge ROS and restore their normal levels. AChE/Aβ-IN-3 can be used in the study of neurological diseases, such as Alzheimer's disease.

N-Caffeoyldopamine (Compound 6i) is an amyloid-beta aggregation inhibitor. N-Caffeoyldopamine can inhibit Aβ aggregation to form nano-rod-like structures, thereby preventing β-sheet formation. N-Caffeoyldopamine can be used for Alzheimer's disease research.

MAO-B-IN-54 is a selective, reversible and competitiv monoamine oxidase B (MAOB) inhibitor with a human IC₅₀ of 0.052 μM and a K_i of 0.028 μM. MAO-B-IN-54 shows weak activity MAOA. MAO-B-IN-54 occupies both the entrance and substrate cavity of MAOB, forming hydrophobic and hydrogen bonding interactions. MAO-B-IN-54 inhibits Aβ aggregation and ROS production. MAO-B-IN-54 can be used for the research of Alzheimer’s disease.

Cannflavin A (Standard) is the analytical standard of Cannflavin A. This product is intended for research and analytical applications. 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.

AZ3971 is an orally active, blood-brain barrier permeable BACE1 inhibitor that does not affect the activity of γ-secretase. AZ3971 reduces the production of Aβ. AZ3971 can be used for the research of Alzheimer's disease.

D-Trp-Aib is a dipeptide and amyloid-β inhibitor with a K_d of 29.6 nM. D-Trp-Aib triggers formation of non-toxic, non-β-sheet, amorphous amyloid β clusters from misfolded amyloid β monomers and toxic amyloid β oligomers, and reduces toxic amyloid β_1-42 deposits. D-Trp-Aib inhibits amyloid fibril formation of α‑synuclein, IAPP and calcitonin. D-Trp-Aib can be used for the research of Alzheimer's disease.

Aβ aggregation-IN-4 can alleviate the neurotoxicity of amyloid-β protein (Aβ) and significantly reduce the level of oligomeric complexes of Aβ (Aβ-OCs). Aβ aggregation-IN-4 does not decrease the level of amyloid-β protein (Aβ). Aβ aggregation-IN-4 attenuates Aβ oligomerization and prevents oligomer-induced death of primary cortical neurons. Aβ aggregation-IN-4 can be used for the study of Alzheimer’s disease (AD).

Aβ-IN-7 (compound 5a) is a potent inhibitor of the Aβ aggregation. Aβ-IN-7 with 50 μM stabilize Aβ monomers in the small oligomeric species and prolong the nucleation process. Aβ-IN-7 inhibits Aβ fibril formation better than Aβ-IN-8 (HY-149583) in 50 μM.

Dyclonine-d₉ hydrochloride (Dyclocaine-d₉ hydrochloride) is the deuterated-labeled Dyclonine hydrochloride (HY-B0364A). Dyclonine hydrochloride (Dyclocaine hydrochloride) is an orally active, blood-brain barrier-permeable piperidine phenylacetone small molecule commonly used as a local anesthetic. Dyclonine hydrochloride acts as a highly selective allosteric antagonist of TRPV3; it also reversibly inhibits G9a, ALDH2 and ALDH3A1, non-competitively blocks AChE. Dyclonine hydrochloride activates the Nrf2/ARE pathway, relieves the epigenetic silencing of FXN, blocks Aβ42 aggregation, and promotes remyelination and reparative polarization of microglia. Dyclonine hydrochloride alleviates pruritus via TRPV3 inhibition; it is used in studies of neurodegenerative disease models based on its AChE inhibitory, antioxidant and remyelinating effects; it sensitizes drug-resistant tumors through ALDH inhibition, and combined use with protease inhibitors induces more tumor cell apoptosis; it inhibits Candida albicans in vitro. Dyclonine hydrochloride can be used for research on multiple diseases including neurodegenerative diseases, cancer and pruritic dermatitis.