Amyloid-β Inhibitor

L-Norvaline is the inhibitor for arginase, that promotes the production of NO, reduces oxidative stress, improves insulin resistance, and exhibits antioxidant and anti-hyperglycemic effects. L-Norvaline can be used in research of Alzheimer’s disease.

Dihydroergocristine mesylate (DHEC mesylate) is a inhibitor of γ-secretase (GSI), reduces the production of the Alzheimer's disease amyloid-β peptides, binds directly to γ-secretase and Nicastrin with equilibrium dissociation constants (K_d) of 25.7 nM and 9.8 μM, respectively.

Ponicidin (Rubescensine B) is an orally active RIPK1 inhibitor with a K_d value of 135 nM. Ponicidin inhibits the JAK2/STAT3 pathway to induce apoptosis, activates the PI3K/Akt pathway, upregulates SIRT1 expression, alleviates oxidative stress, suppresses inflammatory responses and necroptosis, and blocks cell cycle progression. Ponicidin induces ROS production to exert antiproliferative and antiviral effects, while also improving cognitive function and reducing Aβ plaque deposition. Ponicidin can be used in studies related to hepatocellular carcinoma, Alzheimer's disease, and gastric cancer.

Pyridoxal 5'-phosphate hydrate, the active form of vitamin B6, is an essential cofactor for multiple enzymes, including aromatic l-amino acid decarboxylase that catalyzes the final stage in the production of the neurotransmitters dopamine and serotonin. Pyridoxal 5'-phosphate hydrate is the most important coenzyme variant in the process of vitamin B6 intracellular phosphorylation and is interconvertible with other variants, including pyridoxine 5′‐phosphate (PNP) and pyridoxamine 5′-phosphate (PMP).

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.

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

β-Amyloid peptide(16-20) is a amino acid sequences (KLVFF) of Amyloid-β (Abeta). β-Amyloid peptide(16-20) is an effective inhibitor of Abeta fibril formation, with RG-/-GR-NH₂ residues added at N- and C-terminal ends to aid solubility).

Davunetide is an eight amino acid snippet derived from activity-dependent neuroprotective protein (ADNP), a neurotrophic factor that exists in the mammalian CNS. Davunetide possesses neuroprotective, neurotrophic and cognitive protective roperties. Davunetide, a microtubule-stabilizing peptide, interacts with and stabilises neuron-specific βIII-tubulin in vitro. Davunetide penetrates the blood-brain barrier and is non-toxic. Davunetide inhibits Aβ aggregation and Aβ-induced neurotoxicity.

Umibecestat (CNP520) is a selective, orally active BACE inhibitor, with an IC₅₀ of 11 nM for hBACE-1, 10 nM for mouse BACE-1, and 30 nM for hBACE-2. Umibecestat reduces β-Amyloid levels in the brain and cerebrospinal fluid, decreases β-amyloid plaque deposition, and inhibits plaque-associated neuroinflammation. Umibecestat is used in research related to Alzheimer's disease.

Ginsenoside Rg2 is one of the major active components of ginseng. Ginsenoside Rg2 inhibits VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS). Ginsenoside Rg2 also reduces Aβ_1-42 accumulation.

Scyllo-Inositol is an inhibitor that targets the aggregation of misfolded proteins (such as α-synuclein and Amyloid-β), is orally effective, and can cross the blood-brain barrier. Scyllo-Inositol can selectively bind to and stabilize non-toxic oligomers, preventing them from converting into toxic fibers, exerting protein homeostasis regulation and neuroprotective activity. Scyllo-Inositol binds to the hydrophobic region of pathogenic proteins, inhibits protein aggregation, and promotes lysosome- and proteasome-mediated degradation pathways, thereby reducing neurotoxicity. Scyllo-Inositol can be used in the study of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and Huntington's disease.

δ-Secretase inhibitor 11 (compound 11) is an orally active, potent, BBB-penetrated, non-toxic, selective and specific δ-secretase inhibitor, with an IC₅₀ of 0.7 μM. δ-Secretase inhibitor 11 interacts with both the active site and allosteric site of δ-secretase. δ-Secretase inhibitor 11 attenuates tau and APP (amyloid precursor protein) cleavage. δ-Secretase inhibitor 11 ameliorates synaptic dysfunction and cognitive impairments in tau P301S and 5XFAD transgenic mouse models. δ-Secretase inhibitor 11 can be used for Alzheimer's disease research.

Oleanonic acid (3-Oxooleanolic acid) is an orally available triterpene that has anti-inflammatory and insecticidal properties. In vitro, oleanonic acid can improve oxidative stress, autophagy defects, ferroptosis, mitochondrial damage, and endoplasmic reticulum stress induced by Amyloid-β, and in vivo, it can alleviate myocardial hypertrophy in rats.

Birtamimab (NEOD001) is an investigational monoclonal antibody that specifically and selectively target and clear the amyloid. Birtamimab can be used for the research of light chain amyloidosis.

Verbenalin is an orally active terpenoid glycoside that can be extracted from the medicinal plant Verbena officinalis. Verbenalin has anti-inflammatory, antiviral, and neuroprotective effects. Verbenalin has a strong binding affinity to the nsp-12 protein of the SARS-CoV-2 virus. Verbenalin can be used in the research of inflammatory and nervous system diseases such as hepatitis and Alzheimer's disease.