Aloenin (Aloenin A) is a class of anthraquinones isolated from Aloe arborescens. Aloenin has potent peroxyl radical-scavenging activities and moderate inhibitory active on β-secretase (BACE)[1][2].
Scoulerine ((-)-Scoulerine), an isoquinoline alkaloid, is a potent antimitotic compound. Scoulerine is also an inhibitor of BACE1 (ß-site amyloid precursor protein cleaving enzyme 1). Scoulerine inhibits proliferation, arrests cell cycle, and induces apoptosis in cancer cells[1].
BACE1-IN-6 is a BACE1 inhibitor with an IC50 value of 1.5 nM.
JNJ-67569762 is a selective BACE1 inhibitor targeting the S3 pocket (IC50 = 2.7 nM).
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[1].
Aloeresin D is a chromone glycoside isolated from Aloe vera, inhibits β-Secretase (BACE1) activity, with an IC50 of 39 μM[1].
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[1][2].
Sophoflavescenol is a prenylated flavonol, which shows great inhibitory activity with IC50 of 0.013 μM against Phosphodiesterase 5 (PDE5), and also inhibits RLAR, HRAR, AGE, BACE1, AChE and BChE with IC50s of 0.30 µM, 0.17 µM, 17.89 µg/mL, 10.98 µM, 8.37 µM and 8.21 µM, respectively.
β-Secretase Inhibitor II is a β-Secretase inhibitor. β-Secretase Inhibitor II is a simple tripeptide aldehyde (IC50=700 nM for inhibition of total Aβ and IC50=2.5 μM for Aβ1–42). β-Secretase Inhibitor II can be used for the research of Alzheimer's disease[1].
LX2343 is a BACE1 enzyme inhibitor with an IC50 value of 11.43±0.36 μM. LX2343 acts as a non-ATP competitive PI3K inhibitor with an IC50 of 15.99±3.23 μM. LX2343 stimulates autophagy in its promotion of Aβ clearance.
(1α,1'S,4β)-Lanabecestat ((1α,1'S,4β)-AZD3293) is a Beta site APP Cleaving Enzymel (BACE1) inhibitor extracted from patent WO2012087237A1, compound 20a, has IC50s of 2.2 nM (TR-FRET assay) and 0.28 nM (sAPPp release assay), respectively[1].
Cassiaside is a naphthopyrone glucoside, shows mixed-type inhibition against BACE1 (IC50=4.45 μM; Ki=9.85 μM). Cassiaside possesses potential anti- Alzheimer's disease (AD) activity[1].
LY2886721 is an BACE inhibitor used for the treatment of Alzheimer's Disease.IC50 value:Target: BACELY2886721 is a novel potent agent that is used to treat Alzheimer’s Disease in preclinical experiments. LY2886721 is under clinical study. A Safety Study of LY2886721 Multiple Doses is performing in Healthy Subjects.
AM-6494 is a potent and orally active BACE1 (efficacious β-site amyloid precursor protein cleaving enzyme 1) inhibitor (IC50=0.4 nM) with in vivo selectivity over BACE2 (IC50=18.6 nM)[1].
AZD3839 (free base) is a potent and selective BACE1 inhibitor with IC50 of 23.6 uM, about 14-fold selectivity over BACE2, also a β-secretase enzyme inhibitor.target: BACE1, β-secretase enzyme [1]IC50: 23.6 uM [1]AZD3839 dissolved in 0.33% dimethylsulfoxideIn vitro: AZD3839 and its metabolites M1 and M2 inhibited CYP3A4 in a reversible and an irreversible manner, which could affect not only the metabolism of other CYP3A4 substrates but also the metabolism of AZD3839 itself. [1]In vivo: AZD3839 is dissolved in 0.3 M gluconic acid, adjusted to pH 3. Solutions of 0.75, 2.5, and 7.5 mg/ml are prepared and are administered orally by gavage at 2 ml/kg body weight at 1.5, 5, and 15 mg/kg (study 1) and 15 mg/kg (study 2). [1]AZD3839 effectively reduces the levels of Aβ in brain, CSF, and plasma in several preclinical species. [2]
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[1].
BACE-IN-1 (Compound 13) is a substituted lmidazo[1 ,2-a]pyridine derivative which can inhibit β-site amyloid precursor protein-cleaving enzyme (BACE) and that may be useful in the treatment of diseases in which BACE is involved, such as Alzheimer's disease.
RE (EDANS) EVNLDAEFK (DABCYL) R is an EDANS and DABCYL double-labeled peptide，serves as a fluorescent substrate for BACE1(Em=360nm，Ex=528nm). RE (EDANS) EVNLDAEFK (DABCYL) R can be used for BACE1 activity measurement and the enzyme activity level is directly proportional to the fluorescence reaction[1].
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.
SEVNLDAEFR is a substrate for BACE1[1].
Deoxyneocryptotanshinone, a natural tanshinone, is a high affinity BACE1 (Beta-secretase) inhibitor with an IC50 value of 11.53 μM. Deoxyneocryptotanshinone shows a promising dose-dependent inhibition of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 133.5 μM. Deoxyneocryptotanshinone can be used for Alzheimer's disease research[1][2].
Epiberberine chloride, a natural alkaloid, is a BACE1 inhibitor, which also exhibits inhibition activity on CYP2D6 and aldose reductase, alpha-adrenoceptors, acetylcholinesterase (AChE), butyrylcholinesterase, and b-site amyloid precursor protein cleaving enzyme 1.
BACE1-IN-1 is a potent and highly brain penetrant BACE1 inhibitor with IC50s of 32 and 47 nM for human BACE1 and BACE2, respectively.
β-Secretase Inhibitor I is an extremely potent β-secretase inhibitor with reduced cardiovascular and liver toxicity.
Elenbecestat (E2609) is a novel potent BACE-1 inhibitor for the treatment of Alzheimer's disease (AD)[1].
NB-360 is a potent, brain penetrable, and orally bioavailable dual BACE1/BACE2 inhibitor (IC50: mouse and human BACE1=5 nM; BACE2=6 nM). NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in amyloid precursor protein(APP) transgenic mice. NB-360 can completely block the progression of Aβ deposition in the brains of APP transgenic mice. NB-360 shows excellent selectivity over the related aspartyl proteases pepsin, cathepsin D and cathepsin E[1][2].
BACE1/2-IN-1 (compound 34) is a potent BACE1 and BACE2 inhibitor, with an IC50 of 0.01 and 0.0053 μM, respectively. BACE1/2-IN-1 shows a combination of lower Pgp efflux ratio and improved passive permeability. BACE1/2-IN-1 displays reduced liver microsomal metabolic stability[1].
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[1].
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[1].
Kushenol C, isolated from the roots of Sophora flavescens, shows anti-Inflammatory and anti-oxidative stress activities. Kushenol C inhibits BACE1 (β-site APP cleaving enzyme 1) with an IC50 of 5.45 µM[1][2].