Beta-secretase Inhibitor

Bace2 Rat Pre-designed siRNA Set A contains three designed siRNAs for Bace2 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.

BI 1181181 MZ is a potent and selective BACE1 inhibitor. BI 1181181 MZ can be used in the research for Alzheimer’s disease.

GL189 is a β-secretase inhibitor. GL189 has neuroprotective effect, and can be used for research of neurodegenerative diseases.

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.

BACE1-IN-13 (Compound 36) is an orally active BACE1 inhibitor with an IC₅₀ value of 2.9 nM. BACE1-IN-13 is highly potent in hAβ42 cell (IC₅₀ = 1.3 nM). BACE1-IN-13 has cardiovascularly safty and elicits sustained Aβ42 reduction in mouse and dog animal models.

NB-533 is an orally active and brain-penetrant BACE-1 inhibitor with a human IC₅₀ of 0.002 μM. NB-533 also inhibits human cathepsin D with an IC₅₀ of 0.001 μM. NB-533 inhibits amyloidogenic amyloid precursor protein (APP) processing and reduces Aβ₄₀ release. NB-533 reduces brain levels of APP metabolite C99 and Aβ₄₀ in transgenic mice. NB-533 can be used for the research of Alzheimer’s disease.

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

AChE/BChE-IN-38 is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (IC₅₀ = 1.22 μM and 0.40 μM; K_i = 0.94 μM and 0.60 μM). AChE/BChE-IN-38 decreases BACE1 and HTR6 mRNA expression in neuroblastoma cells. AChE/BChE-IN-38 improves cognitive and behavioral parameters in a Scopolamine-induced Alzheimer's disease zebrafish model. AChE/BChE-IN-38 is useful for research on Alzheimer's disease.

JNK3/Wnt/β-catenin modulator-1 is a brain-penetrant JNK3 inhibitor and Wnt/β-catenin activator. JNK3/Wnt/β-catenin modulator-1 decreases Aβ_1-42 production and reduced ROS generation. JNK3/Wnt/β-catenin modulator-1 inhibits the activation of JNK and Puma, promotes Beclin-1 expression, reduces GSK-3β and BACE1 expression and activates Wnt/β-catenin signaling. JNK3/Wnt/β-catenin modulator-1 improves cognitive and memory performance, attenuates histopathological brain damage, preserves structure of hippocampal pyramidal cells and cerebral cortical neurons. JNK3/Wnt/β-catenin modulator-1 can be used for the research of Alzheimer's disease.

BACE-IN-3 (Example 3) is a BACE inhibitor, with an IC₅₀ of 0.004 μM.

NB-216 is an orally active and brain-penetrant BACE-1 inhibitor (IC₅₀ = 17 nM). NB-216 has a strong inhibitory effect on cathepsin D (IC₅₀ = 1 nM) and cathepsin E (IC₅₀ = 0.4 nM). NB-216 can be used for the study of Alzheimer's disease.

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

Multitarget AD-IN-8 is a blood-brain barrier-penetrant, orally active multitarget inhibitor. Multitarget AD-IN-8 inhibits abnormal Tau phosphorylation at Thr181 and Ser396 sites and attenuates NF-κB phosphorylation. Multitarget AD-IN-8 downregulates BACE1 expression to reduce Aβ production, inhibits the Bax/Bcl-2 pathway, and suppresses Caspase-1 activation. Multitarget AD-IN-8 attenuates p38, ERK1/2, and JNK phosphorylation and inhibits Aβ_25-35-induced Apoptosis. Multitarget AD-IN-8 exhibits neuroprotective effects against Aβ_25-35-induced injury, ameliorates learning and memory deficits in AD mouse models, and alleviates hippocampal neuronal pathological damage. Multitarget AD-IN-8 can be used for research on Alzheimer's disease.

AChE/BChE/BACE-1-IN-2 (Compound 4o) is an orally active inhibitor of AChE, BChE, and BACE-1 with IC₅₀ values of 0.069, 0.127 and 0.097 μM against hAChE, hBChE and hBACE-1, respectively. AChE/BChE/BACE-1-IN-2 shows considerable PAS-AChE binding capability, excellent brain permeation, potential disassembly of Aβ aggregates, and neuroprotective activity against Aβ-induced stress. AChE/BChE/BACE-1-IN-2 has remarkable antioxidant potential.

BACE1-IN-14 (compound 27f) is a BACE1 inhibitor, with the EC₅₀ values of 0.7 μM and 1.6 μM for BACE1 and BACE2. BACE1-IN-14 is can be used in Alzheimer's disease (AD) research.

COX-2-IN-22 (Compound 4h) is a COX-2 inhibitor with an IC₅₀ of 8.6 µM. COX-2-IN-22 also inhibits AChE, BChE, β-Secretase, LOX-5 and DPPH with IC₅₀ values of 2.8, 6.3, 15.3, 13.9 and 6.8 µM, respectively. COX-2-IN-22 can cross BBB.

BACE1-IN-8 (compound 70b) is a potent BACE1 (β-site APP cleaving enzyme 1) inhibitor, with an IC₅₀ of 3.9 µM.

TAK-070 hydrochloride hydrate is a noncompetitive and orally active BACE1 inhibitor (IC₅₀ = 3.15 μM). TAK-070 hydrochloride hydrate can be used for research of Alzheimer’s disease (AD). TAK-070 hydrochloride hydrate inhibits brain levels of soluble Aβ, and improves cognitive impairments in AD model.

Multitarget AD inhibitor-1 is a selective and reversible butyrylcholinesterase (BuChE) inhibitor with IC₅₀s of 7.22 μM and 1.55 μM for hBuChE and eqBuChE (BuChE from equine serum), respectively. Multitarget AD inhibitor-1 inhibits β-secretase (IC_50hBACE-1=41.60 μM), amyloid β aggregation (IC_50Aβ=3.09 μM), tau aggregation. Multitarget AD inhibitor-1, a diphenylpropylamine derivative, has the potential for multifunctional disease-modifying anti-Alzheimer’s research.

BACE1-IN-15 (Compound 72) is a selective inhibitor of beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with oral activity and the ability to penetrate the blood-brain barrier. Its IC₅₀ value is 121.65 nM (the IC₅₀ value for BACE-2 is 480.92 nM). BACE1-IN-15 can be used in the research of the Alzheimer's disease field