bace1

BACE1-IN-1 is a high brain penetrant BACE1 inhibitor (IC50s: 32 and 47 nM for human BACE1 and BACE2).

BACE1/2-IN-1 (compound 34) is an effective BACE1 and BACE2 inhibitor with IC50 of 0.01 and 0.0053 μM, respectively. BACE1/2-IN-1 has lower Pgp efflux ratio and improved passive permeability. The metabolic stability of BACE1/2-IN-1 in liver microsomes is decreased.

AChE/BACE1/GSK3β-IN-1 is an orally active, blood-brain barrier-transparent, moderately bioavailable triple inhibitor of AChE/BACE1/GSK3β. AChE/BACE1/GSK3β-IN-1 can be used to study Alzheimer's disease (AD).

BACE-IN-1 acetate (BACE-IN-1 acetate (350228-37-4，Free base)) has been used as β-site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) inhibitor in BACE1 inhibitor assay. β-Site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1), an aspartic protease belongs to the protease family of enzymes comprises of six luminal cysteine residues. These residues help in the formation of three intermolecular disulfide bonds and N-linked glycosylation sites.

BACE1-IN-13 (Compound 36), an orally active inhibitor of BACE1, exhibits high potency with an IC50 of 2.9 nM and demonstrates greater efficacy in hAβ42 cells (IC50 = 1.3 nM). It is considered safe for the cardiovascular system and induces a sustained reduction of Aβ42 in both mouse and dog animal models [1].

BACE1-IN-10 is a potent inhibitor of BACE1, demonstrating sub-micromolar activity against recombinant BACE1 (rBACE1) [1].

BACE1-IN-2 is a BACE1 inhibitor (IC50: 22 nM).

BACE1-IN-8 is a potent inhibitor of BACE1 (β-site APP lyase 1) (IC50: 3.9 μM).

BACE1-IN-6 is a BACE1 inhibitor with an IC 50 value of 1.5 nM.

BACE1-IN-12 is a potent BACE1 inhibitor (IC50: 8.9 μM) that can cross the blood-brain barrier. BACE1-IN-12 selectively inhibits BuChE (butylcholinesterase) activity (IC50: 3.2 μM). BACE1-IN-12 has potential for anti-Alzheimer's disease studies.

BACE1-IN-4 is a potent and highly selective BACE1 inhibitor (IC50: 3.8 nM; Ki: 1.9 nM), more selective at BACE1 over BACE2.

BACE1-IN-5 (Compound 15), a potent β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor, demonstrates significant efficacy with an IC50 of 9.1 nM for BACE1 inhibition and an impressive IC50 of 0.82 nM against cellular amyloid-β (Aβ) production. Additionally, it is engineered to enhance hERG inhibition and P-gp efflux, indicating its optimized medicinal chemistry profile [1].

BACE-1 inhibitor 1 (Compound 8a) is an effective BACE-1 inhibitor (IC50: 56 nM).

AChE/BChE/BACE-1-IN-2 (Compound 4o) exhibits remarkable antioxidant potential and considerable binding capability towards PAS-AChE. AChE/BChE/BACE-1-IN-2 is an orally active AChE, BACE-1 and BChE inhibitor with IC 50 values of 0.069, 0.097 and 0.127 μM against hAChE, hBACE-1 and hBChE, respectively. AChE/BChE/BACE-1-IN-2 shows potential disassembly of Aβ aggregates and neuroprotective activity against Aβ-induced stress with excellent brain permeation [1].

BACE-IN-1 is an imidazo[1,2-a]pyridine derivative that inhibits the β-site amyloid precursor protein cleavage enzyme (BACE) sentence.BACE-IN-1 has the potential to investigate diseases involving BACE, such as Alzheimer's disease.

BACE-1 Inhibitor 2 is a potent, CNS-permeable inhibitor of BACE-1, exhibiting an IC50 value of 1.5 nM in enzymatic assays [1].

AChE/BChE/BACE-1-IN-1 (Compound 4k) is an orally active inhibitor that targets acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1). It displays IC50 values of 0.058 μM, 0.082 μM, and 0.115 μM against hAChE, hBChE, and hBACE-1, respectively. AChE/BChE/BACE-1-IN-1 exhibits significant binding affinity with PAS-AChE, excellent ability to cross the blood-brain barrier, potential disassembly of amyloid-beta (Aβ) aggregates, and neuroprotective properties against Aβ-induced stress. Moreover, AChE/BChE/BACE-1-IN-1 demonstrates remarkable antioxidant capabilities [1].

Phytic acid dipotassium salt is an endogenous metabolite that inhibits β-secretase 1 (BACE1).

Loganin (Loganoside), an iridoid glucoside, has been reported to be an inhibitor of Cox-1 and also noted to suppress TNF-α formation. This compound also has displayed potent free-radical-scavenging activity and inhibitory effects on melanogenesis.

Sophoflavescenol is a mixed inhibitor of PDE5 with a K(i) value of 0.005 microM. Sophoflavescenol has antioxidant, anti-inflammatory, and apoptotic effects , these effects might contribute to the antitumor activity without severe side effects. Sophoflaves

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.

JNJ-67569762 is a selective BACE1 inhibitor targeting the S3 pocket ( IC 50 = 2.7 nM).

Kushenol C is a good 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenger, and it exhibits inhibitory activity against Sodium-dependent glucose cotransporter 2(SGLT2). Kushenol C shows antimicrobial activity against Staphylococcus aureus and Streptococcus mutan

BuChE-IN-8 (compound 19c), a butyrylcholinesterase (BuChE) inhibitor, exhibits an IC50 value of 559 nM and concurrently inhibits human β-secretase (BACE1) and Aβ40 aggregation. It also demonstrates notable antiamnesic properties [1].

AM-6494 is a potent and orally active BACE1 inhibitor (IC50: 0.4 nM) with in vivo selectivity over BACE2 (IC50: 18.6 nM).

Lanabecestat (AZD3293) is a highly potent and highly permeable, orally active BACE1 inhibitor (Ki: 0.4 nM) that crosses the blood-brain barrier, Lanabecestat can be used for the study of neurological diseases like Alzheimer's disease.

OM99-2 is an eight-residue peptidomimetic with a high affinity for human brain memapsin 2, exhibiting a Ki value of 9.58 nM. This compound represents a significant advancement in the development of BACE1 inhibitors and holds potential for the study of Alzheimer's disease.

6,9-Dichloro-1,2,3,4-tetrahydroacridine is a synthetic intermediate in the synthesis of tacrine-based acetylcholinesterase (AChE) inhibitors.1It is also an intermediate in the synthesis of multifunctional tacrine hybrids that possess radical scavenging, amyloid-β aggregation inhibitory, and/or β-secretase 1 (BACE1) inhibitory activities in addition to their activity as AChE inhibitors.2,3 1.Recanatini, M., Cavalli, A., Belluti, F., et al.SAR of 9-amino-1,2,3,4-tetrahydroacridine-based acetylcholinesterase inhibitors: Synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analoguesJ. Med. Chem.43(10)2007-2018(2000) 2.Digiacomo, M., Chen, Z., Wang, S., et al.Synthesis and pharmacological evaluation of multifunctional tacrine derivatives against several disease pathways of ADBioorg. Med. Chem. Lett.25(4)807-810(2015) 3.Li, S.Y., Jiang, N., Xie, S.S., et al.Design, synthesis and evaluation of novel tacrine-rhein hybrids as multifunctional agents for the treatment of Alzheimer's diseaseOrg. Biomol. Chem.12(5)801-814(2014)

Potent and selective β-secretase (BACE) inhibitor (IC50 values are 10.2 and 20.3 nM for human BACE2 and BACE1, respectively). Displays >5,000-fold selectivity for BACE over other proteases including cathepsin D, pepsin and renin. Inhibits Aβ1-40 and Aβ1-42 production in cells expressing mutated APP. Reduces hippocampal and cortical Aβ and sAPPβ levels in an Alzheimer's disease mouse model.

Elenbecestat,also known as E2609 is a BACE1 inhibitor. By inhibiting BACE, a key enzyme in the production of Aβ peptides, E2609 decreases the formation of these peptides which can aggregate into toxic oligomers and protofibrils and eventually form amyloid plaques in the brain. Elenbecestat has been shown to reduce Aβ levels in cerebrospinal fluid, was investigated in two global phase 3 studies in early AD.

AZD3839 free base is a potent and selective BACE1 inhibitor with Ki of 26.1 nM, about 14-fold selectivity over BACE2. Phase 1.

AZD-3289, a potent BACE1 inhibitor, is used potentially for the treatment of Alzheimer's disease.

Verubecestat (MK-8931) (MK-8931) is an effective and specific β-secretase inhibitor and β-site APP-cleaving enzyme 1 inhibitor or BACE1 protein inhibitor.

TAK-070 is a non-competitive inhibitor of BACE1.

Questin is an antimicrobial agent derived from Aspergillus florescens with an antimicrobial activity profile that inhibits V. harveyi, V. anguillarum, V. cholerae and V. parahemolyticus with MIC values of 31.25 µg/mL, 62.5 µg/mL, 62.5 µg/mL and 125 µg/mL, respectively. Questin has good potential to inhibit AChE, BChE and BACE1 and may be used in the development of drugs for the treatment or prevention of Alzheimer's disease.

AMG-8718 is a selective, orally active and potent BACE1 inhibitor that acts on both BACE1 (IC50: 0.0007 μM) and BACE2 (IC50: 0.005 μM). AMG-8718 significantly reduces CSF and Aβ40 levels in the brain.

LY2886721, a BACE inhibitor, is used for the therapy of Alzheimer's Disease.

GRL-8234 is a small-molecule BACE1 inhibitor that reverses memory impairments and age-related cognitive decline.

AZD-3839 hemifumarate is a potent and selective BACE1 inhibitor and clinical candidate for the treatment of Alzheimer's disease.

AChE-IN-11 (compound 5C) can be used in the Alzheimer's disease research with neuroprotective effects and good antioxidant activity (ORAC = 2.5 eq). AChE-IN-11 is a good multifunctional agent with IC 50 values of 7.9 μM, 9.9 μM, and 8.3 μM against AChE, MAO-B, and BACE1. AChE-IN-11 has a mixed-type AChE inhibition that can bind to the CAS and PAS of AChE. AChE-IN-11 is also a selective metal ions chelator [1].

Verubecestat tosylate, also known as MK-8931 or SCH 900931, is a potent and selective beta-secretase inhibitor, and BACE1 protein inhibitor or Beta-site APP-cleaving enzyme 1 inhibitor. Verubecestat tosylate is a promising novel therapeutic drug candidate in Alzheimer's disease. Verubecestat tosylate reduced Aβ cerebral spinal fluids (CSF) levels up to 92% and was well tolerated by patients.

Cassiaside is a naphthyl ketone glycoside that inhibits BACE1 (IC50= 4.45 μM; Ki=9.85 μM).Cassiaside exhibits significant hepatoprotective effects against galactosamine injury and has potential anti-Alzheimer's disease (AD) activity.

1. Epiberberine may be caused drug interactions based on CYP2D6 enzyme. 2. Epiberberine has anti-adipogenic effect is mediated by downregulation of the Raf/MEK1/ERK1/2 and AMPKα/Akt pathways during 3T3-L1 adipocyte differentiation. 3. Epiberberine, as the brightest FSA emitter among the alkaloids, can also serve as an efficient conformation probe for HTG DNA and discriminate the DNA G-quadruplex from the RNA counterpart.

Epiberberine chloride, a natural pro-berberine from Coptis chinensis Franch. is an AChE, BChE, and BACE1 inhibitor with IC50 values of 1.07, 6.03, and 8.55 μM, respectively.Epiberberine chloride has antioxidant effects and inhibits the effects of Ca9-22 and Fa2R. Epiberberine chloride has antioxidant effects, inhibits the motility of Ca9-22 and FaDu cell lines, and can be used to study hyperlipidemia, Alzheimer's disease and diabetes.

Auraptene is a coumarin derived from citrus plants that bears a geranyloxyl moiety at its C-7. It has anti-inflammatory, anti-carcinogenic, anti-bacterial, neuroprotective, and hepatoprotective activities. It inhibits leukocyte activation and induces phas

Lanabecestat camsylate is used as a BACE1 Inhibitor.

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

Umibecestat is an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), 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.

8-Geranyloxypsoralen inhibits α2-secretase (BACE1) activity in non-competitive manner, with the IC(50) values <25.0 μM, it can induce vasorelaxation on rat arterial tissues. 8-Geranyloxypsoralen possesses nematicidal activities, the median lethal concentrations (LC(50)) is 188.3 mg L against B. xylophilus and is 117.5 mg L against P. redivivus.

PD07 is an orally active acetylcholinesterase (AChE) inhibitor, exhibiting an IC50 of 0.29 μM against human AChE, and demonstrates inhibition of cholinesterases (ChEs), β-site amyloid precursor protein cleaving enzyme 1 (BACE1) with an IC50 of 13.42 μM, as well as Aβ1–42 aggregation in vitro. Additionally, PD07 possesses antioxidant properties with a DPPH radical inhibition IC50 value of 26.46 μM and has been shown to ameliorate memory and cognitive deficits in scopolamine-induced amnesic rats. This compound is relevant for Alzheimer’s disease research [1].