Beta-secretase Inhibitor

Se-Methylselenocysteine, a precursor of Methylselenol, has potent cancer chemopreventive activity and anti-oxidant activity. Se-Methylselenocysteine is orally bioavailable, and induces apoptosis.

Verubecestat (MK-8931) is an orally active, high-affinity BACE1 and BACE2 inhibitor with K_i values of 2.2 nM and 0.38 nM. Verubecestat effectively reduces Aβ40 and has the potential for Alzheimer's Disease.

LY2886721 is a potent, selective and orally active beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor with an IC₅₀ of 20.3 nM for recombinant human BACE1. LY2886721 is selectivity against cathepsin D, pepsin, and renin, but lacking selectivity against BACE2 (IC₅₀ of 10.2 nM). LY2886721 can across blood-brain barrier and has the potential for Alzheimer's disease treatment.

Epiberberine chloride is an alkaloid isolated from Coptis chinensis, acts as a potent AChE and BChE inhibitor, and a non-competitive BACE1 inhibitor, with IC₅₀s of 1.07, 6.03 and 8.55 μM, respectively. Epiberberine chloride has antioxidant activity, with peroxynitrite ONOO^- scavenging effect (IC₅₀, 16.83 μM), and may protect against Alzheimer disease. Epiberberine chloride inhibits the early stage of differentiation of 3T3-L1 preadipocytes, downregulates the Raf/MEK1/2/ERK1/2 and AMPKα/Akt pathways. Epiberberine has the potential effect in the research of diabetic disease.

BCA (Disodium bicinchoninate) is an orally active and non-competitive Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor with an IC₅₀ value of 28 µM, a K_i value of 43 µM. BCA shows anticancer activity. BCA has the potential for the research of Alzheimer's disease (AD).

Scoulerine ((-)-Scoulerine; Discretamine) hydrochloride is a multi-target inhibitor with anti-tumor and antioxidant activities. Scoulerine hydrochloride mainly targets the PI3K/Akt/mTOR signaling axis and α1D-adrenergic receptor, disrupts microtubule structure, and induces cell cycle arrest and apoptosis. Scoulerine hydrochloride effectively inhibits mitochondrial dehydrogenase activity, targets GABA receptors and BACE1, and suppresses the proliferation, migration, invasion, epithelial-mesenchymal transition and stem cell properties of cancer cells. Scoulerine hydrochloride also exhibits multiple pharmacological activities including anti-Plasmodium falciparum, antibacterial, antiemetic and antitussive effects, and regulates endoplasmic reticulum stress and mitochondrial function (modulates Bax, Bcl-2 and cytochrome c). Scoulerine hydrochloride is applicable to research related to leukemia, ovarian cancer, and colorectal cancer.

GFAP/NF-κB/APOE/NLRP3-IN-1 is an orally active, blood-brain barrier-permeable multi-target inhibitor with an IC₅₀ of 3.50 nM against Acetylcholinesterase. GFAP/NF-κB/APOE/NLRP3-IN-1 inhibits BACE-1 with an IC₅₀ of 14.61 nM. GFAP/NF-κB/APOE/NLRP3-IN-1 inhibits Aβ_1-42 aggregation with an IC₅₀ of 8.63 μM. GFAP/NF-κB/APOE/NLRP3-IN-1 reduces the levels of GFAP, NLRP3 inflammasome, NF-κB and APOE. GFAP/NF-κB/APOE/NLRP3-IN-1 is applicable for the research of Alzheimer's disease and neuroblastoma.

8-geranyloxy-5-methoxypsoralen is a BACE1 inhibitor with an IC₅₀ of 11.1 μM. 8-geranyloxy-5-methoxypsoralen potently inhibits BACE1 activity. 8-Geranyloxy-5-methoxypsoralen can be used for the research of Alzheimer's disease.

Scoulerine ((-)-Scoulerine; Discretamine) hydrochloride is a multi-target inhibitor with anti-tumor and antioxidant activities. Scoulerine mainly targets the PI3K/Akt/mTOR signaling axis and α1D-adrenergic receptor, disrupts microtubule structure, and induces cell cycle arrest and apoptosis. Scoulerine effectively inhibits mitochondrial dehydrogenase activity, targets GABA receptors and BACE1, and suppresses the proliferation, migration, invasion, epithelial-mesenchymal transition and stem cell properties of cancer cells. Scoulerine also exhibits multiple pharmacological activities including anti-Plasmodium falciparum, antibacterial, antiemetic and antitussive effects, and regulates endoplasmic reticulum stress and mitochondrial function (modulates Bax, Bcl-2 and cytochrome c). Scoulerine is applicable to research related to leukemia, ovarian cancer, and colorectal cancer.

Lanabecestat (AZD3293; LY3314814) is a potent, orally active and blood-brain barrier penetrating BACE1 inhibitor with a K_i of 0.4 nM. Lanabecestat is used for the research of Alzheimer's disease.

Elenbecestat (E2609) is a potent, orally bioavailable and BBB-penetrant BACE-1 inhibitor. Elenbecestat has the potential for Alzheimer's disease (AD) research.

Umibecestat (CNP520) is a beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibitor with IC₅₀s of 11 nM and 10 nM for human BACE-1 and mouse BACE-1, respectively. Umibecestat can be used for the research of alzheimer's disease.

BACE2-IN-1 (compound 3l) is a highly selective BACE2 inhibitor with a Kⁱ value of 1.6 nM. BACE2 inhibitors can be used to research of Type 2 Diabetes.

LY2811376 is the first orally available non-peptidic β-secretase (BACE1) inhibitor with IC₅₀ of 239 nM-249 nM, that acts to decrease Aβ secretion with EC₅₀ of 300 nM, and demonstrates to have 10-fold selectivity towards BACE1 over BACE2, and more than 50-fold inhibition over other aspartic proteases including cathepsin D, pepsin, or renin.

β-Secretase Inhibitor IV is a potent, cell-active BACE-1 inhibitor with IC₅₀s of 15.6 and 16.3nM under BACE-1 concentrations of 2 nM and 100 pM, respectively.

Eslicarbazepine acetate (BIA 2-093), an antiepileptic agent, is a dual a dual Inhibitor of β-Secretase and voltage-gated sodium channel.

AZD3839 is an orally available, selective, reversible inhibitor of the β-site amyloid precursor protein cleaving enzyme BACE1 that can cross the blood-brain barrier. AZD3839 inhibits recombinant human BACE1 with a K_i=26.1 nM. AZD3839 inhibits A40 production in SH-SY5Y cells with an IC₅₀ of 4.8 nM. AZD3839 binds to BACE1 and reduces the Aβ amyloid produced by the cleavage of amyloid precursor protein (APP) by BACE1 and γ-secretase. AZD3839 can be used in the field of Alzheimer's disease research.

Eslicarbazepine is an oral anticonvulsant indicated for the adjunctive treatment of partial seizures.

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.

Tenuifolin is effective and has a protective action. Tenuifolin inhibits β-secretase decreases Aβ protein secretion, suppresses Aβ25-35 secretion, and subsequently caspase-3 and caspase-9 become active. Tenuifolin's ability to lower AChE activity, increase at the same time, increase the ability of the upper glands, and improve the ability to read and remember. Research on tenuifolin's potential for use in urinary disease (AD).