aβ40

Begacestat (GSI-953) is a potent and selective gamma-secretase inhibitor (γ-secretase) that inhibits Amyloid-beta production with nanomolar potency, selectively inhibits cleavage of APP in cellular level Notch cleavage assays, reverses situational memory deficits, and can be used to study Alzheimer's disease.

MK-0752, a γ-secretase inhibitor, reduces Aβ40 production(IC50=5 nM).

DC-Chol hydrochloride(DC-Cholesterol hydrochloride) inhibited the formation of Aβ40 fibrils under appropriate experimental conditions and significantly inhibited amyloid formation from oxidized hCT in a dose-dependent manner.DC-Chol hydrochloride induces an improved and balanced immunity, which could contribute to hepatitis B vaccine research.

Tau Aβ40 aggregation-IN-1 (Compound 20) functions as an inhibitor for tau and Aβ 40 aggregation, exhibiting IC50 values of 1.8 μM and 1.3 μM, respectively [1].

LY-411575, a potent γ-secretase inhibitor, is with IC50 of 0.078 nM in the membrane and 0.082 nM in cell-based. It also suppresses Notch clevage with IC50 of 0.39 nM.

BMS 433796 is a γ-secretase inhibitor that demonstrates Aβ-lowering activity in a transgenic mouse model of Alzheimer's disease.

1-Decanesulfonic acid (Decane-1-sulfonic acid) is a potential amyloid beta peptide (Aβ40) inhibitor, useful for studying cardiovascular diseases.

BPN-15606 besylate is a highly potent, orally active γ-secretase modulator, attenuates the production of Aβ40 and Aβ42 by SHSY5Y neuroblastoma cells (IC50s: 7 nM and 17nM).

BPN-15606, an orally active γ-secretase modulator (GSM), significantly reduces Aβ42 and Aβ40 production in SHSY5Y neuroblastoma cells, demonstrating IC50 values of 7 nM and 17 nM, respectively. This compound exhibits favorable pharmacokinetic pharmacodynamic (PK PD) properties, such as bioavailability, half-life, and clearance. Importantly, BPN-15606 markedly decreases Aβ42 and Aβ40 levels in the central nervous system of both rats and mice[1].

12-Crown-4 disrupts Aβ40 fibrils. 12-Crown-4 can enter into the hydrophobic core region and form competitive, hydrophobic interactions with key hydrophobic residues.

Biphenyl-3′,3,4,4′-tetrol (BPT) is a potent inhibitor of Aβ40 aggregation and can be utilized in research related to neurodegenerative diseases such as Alzheimer's.

Itanapraced (CHF5074), a γ-secretase modulator, reduces Aβ42 40 secretion (IC50: 3.6 18.4 μM).

GSK-B, a potent γ-secretase modulator, decreases Aβ42, increases Aβ38 with no effect on Aβ40 levels.

Amyloid-β (1-42) (Aβ42) is a neurotoxic 42-amino acid protein fragment found in amyloid plaques in postmortem cerebral cortex from patients with Alzheimer's disease.1,2,3Aggregation of Aβ42 results in the formation of neurotoxic fibrils or globular oligomers.1Aβ42 accumulates in the brain of many transgenic mouse models of Alzheimer's disease and, in many models, the onset of amyloid deposition positively correlates with deficits in spatial learning and memory.4 1.Wolfe, M.S.Therapeutic strategies for Alzheimer's diseaseNat. Rev. Drug Discov.1(11)859-866(2002) 2.Iwatsubo, T., Odaka, A., Suzuki, N., et al.Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)Neuron13(1)45-53(1994) 3.Hardy, J.A., and Higgins, G.A.Alzheimer's disease: The amyloid cascade hypothesisScience256(5054)184-185(1992) 4.Jankowsky, J.L., and Zheng, H.Practical considerations for choosing a mouse model of Alzheimer's diseaseMol. Neurodegener.12(1)89(2017)

Amyloid-β (1-8, A2V) is a truncated form of amyloid-β (Aβ) that contains a valine to alanine substitution at position 2 of the Aβ numbering convention (Aβ A2V), which corresponds to position 673 of the amyloid precursor protein (APP) numbering convention (APP A673V). An Aβ (1-40) (Aβ40) A2V peptide increases the production of Aβ and the rate and amount of amyloid fibril formation in vitro, effects that can be reduced by coincubation with wild-type Aβ40. Aβ40 and Aβ42 levels are increased in CHO cells expressing the Aβ A2V mutation and in fibroblasts derived from patients with the Aβ A2V mutation. As a homozygous mutation, Aβ A2V is correlated with Alzheimer's disease with distinctive pathological features, but disease does not develop in patients with a heterozygous Aβ A2V mutation.

Glycerophosphorylethanolamine is an active phosphodiester metabolite of phosphatidylethanolamine.1,2It promotes aggregation of amyloid-β (1-40) (Aβ40)in vitro, and levels of glycerophosphorylethanolamine are elevated in postmortem brains isolated from patients with Alzheimer's disease. 1.Klunk, W.E., Xu, C.J., McClure, R.J., et al.Aggregation of β-amyloid peptide is promoted by membrane phospholipid metabolites elevated in Alzheimer's disease brainJ. Neurochem.69(1)266-272(1997) 2.Blusztajn, J.K., Lopez Gonzalez-Coviella, I., Logue, M., et al.Levels of phospholipid catabolic intermediates, glycerophosphocholine and glycerophosphoethanolamine, are elevated in brains of Alzheimer's disease but not of Down's syndrome patientsBrain Res.536(1-2)240-244(1990)

1,2-Dipalmitoyl-13C-sn-glycero-3-PC is intended for use as an internal standard for the quantification of 1,2-dipalmitoyl-sn-glycero-3-PC by GC- or LC-MS. 1,2-Dipalmitoyl-sn-glycero-3-PC (DPPC) is a zwitterionic glycerophospholipid commonly used in the formation of lipid monolayers, bilayers, and liposomes for use in a variety of applications.1,2,3,4 It has been used in the formation of proteoliposomes for implantation of γ-glutamyl transpeptidase into human erythrocyte membranes.3 Incorporation of glycosphingolipid antigens into DPPC-containing liposomes increases the immunogenicity of the antigens in mice.4 |1. Ege, C., and Lee, K.Y.C. Insertion of Alzheimer's Aβ40 peptide into lipid monolayers. Biophys. J. 87(3), 1732-1740 (2004).|2. Leekumjorn, S., and Sum, A.K. Molecular simulation study of structural and dynamic properties of mixed DPPC/DPPE bilayers. Biophys. J. 90(11), 3951-3965 (2006).|3. Kalra, V.K., Sikka, S.C., and Sethi, G.S. Transport of amino acids in γ-glutamyl transpeptidase-implanted human erythrocytes. J. Biol. Chem. 256(11), 5567-5571 (1981).|4. Uemura, A., Watarai, S., Iwasaki, T., et al. Induction of immune responses against glycosphingolipid antigens: Comparison of antibody responses in mice immunized with antigen associated with liposomes prepared from various phospholipids. J. Vet. Med. Sci. 67(12), 1197-1201 (2005).

Semagacestat (LY450139) (LY450139) is a γ-secretase blocker for Aβ42 Aβ40 Aβ38 (IC50: 10.9 12.1 12.0 nM) and also inhibits Notch signaling (IC50: 14.1 nM).

Avagacestat (BMS-708163) (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.

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.

RO4929097 (RG-4733), a γ secretase inhibitor (IC50: 4 nM), inhibits cellular processing of Aβ40 and Notch (EC50: 14 5 nM).

BPN-15606 besylate is a potent, orally active γ-secretase regulator (GSM) that reduces the production of Aβ42 (IC50: 7 nM) and Aβ40 (IC50: 17 nM) by SHSY5Y neuroblastoma cells. BPN-15606 besylate exhibited good PK PD properties (including bioavailability, half-life and clearance).

Gamma-secretase modulator 5 (compound 22d) is a gamma-secretase modulator (GSM) that crosses the blood-brain barrier and inhibits the production of the aggregated amyloid β peptide Aβ42 (IC50: 60 nM). This compound is valuable for studying 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.