γ-secretase

γ-Secretase modulator 13 is a γ-secretase modulator (GSMs) that inhibits the production of amyloid β-peptide Aβ42 and can be used to study Alzheimer's disease and tumors.

gamma-secretase modulator 1 is a modulator of γ secretase and can be used in studies about the treatment of Alzheimer's disease.

BACE-IN-1 is amyloid precursor protein beta-secretase inhibitor

β-Secretase Inhibitor I is a highly potent inhibitor of the β-secretase enzyme. This compound exhibits exceptional inhibitory activity while also demonstrating a significant reduction in cardiovascular and liver toxicity.

γ-Secretase modulator 4 is a potent γ-secretase modulator, reduces the Aβ42 level with IC50s of 0.017 μM and 0.014 μM in mouse and human, respectively.

γ-Secretase modulator 10 is a novel γ-secretase modulator.

γ-Secretase-IN-1 is a potent γ-secretase inhibitor that displays partial antiproliferative activity on T-47D cells and inhibits β-amyloid(40), β-amyloid(42), and Notch γ-secretase cleavage.

γ-Secretase modulator 12 (Compound 1a) is a selective compound that effectively reduces amyloid-β42 (Aβ42) levels with an IC50 of 0.39 μM. It is specifically designed for Alzheimer's disease research. Notably, γ-Secretase modulator 12 exhibits a favorable brain/plasma ratio (Kp, brain = 0.72) in mice [1].

gamma-Secretase Modulators serves as a useful treatment for Alzheimer's disease by inhibiting the production of Amyloid-β. Specifically, it acts as a gamma-Secretase Modulators with an IC50 value.

gamma-secretase modulator 5 (compound 22d) is a gamma-secretase modulator (GSMs) that crosses the blood-brain barrier and exhibits an inhibitory effect on the production of the aggregated amyloid β peptide Aβ42 (IC50: 60 nM). gamma-secretase modulator 5 can be used in the study of Alzheimer's disease. The gamma-secretase modulator 5 can be used to study Alzheimer's disease.

γ-Secretase modulator 11 hydrochloride is a potent, orally active γ-secretase modulator (IC50: 0.029 μM). γ-Secretase modulator 11 hydrochloride significantly reduces brain Aβ42 levels and rescues the cognitive deficits exhibited by AD model mice. γ-Secretase modulator 11 hydrochloride has shown research potential in Alzheimer's disease.

β-Secretase Inhibitor III is a highly selective inhibitor of BACE1 with a Ki value of 0.13 nM.

β-Secretase Inhibitor II is a tripeptide aldehyde compound that acts as an inhibitor of β-Secretase. It exhibits a simple structure and has an inhibitory potency of IC50 = 700 nM against total Aβ and IC50 = 2.5 μM specifically against Aβ 1-42. This compound is particularly useful in research related to Alzheimer's disease.

δ-secretase inhibitor 11 is an inhibitor of δ-secretase and can be used as a lead compound for translational development of AD treatment.

5-{8-[(3,4'-Difluoro[1,1'-biphenyl]-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridin-3-yl}-N-methylpyridine-2-carboxamide (1o) exhibited high in vitro potency and brain exposure, was able to cause a significant reduction in brain Aβ42 levels, and had no inhibitory effect on cytochrome p450 enzymes. In addition, compound 1o exhibited excellent anti-cognitive deficits in AD model mice.

Z-Ile-Leu-aldehyde is an effective and competitive peptide aldehyde inhibitor of γ-secretase and notch.

gamma-secretase inhibitior-1 is a gamma-secretase modulator that is useful to Alzheimer's disease [1].

Gamma-secretase modulator 2 is a potent, selective compound for the treatment of Alzheimer's disease, specifically designed to modulate γ-secretase activity. This modulation selectively attenuates the production of Aβ(1-42), addressing diseases associated with Aβ deposition in the brain, particularly Alzheimer's disease.

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).

gamma-secretase modulator 3 is a gamma-secretase modulator.

DAPT (LY-374973) is a γ-secretase inhibitor that inhibits total Aβ and Aβ42 (IC50=115/200 nM) and is orally active. DAPT is also a Notch inhibitor. DAPT induces cell differentiation, autophagy and apoptosis.

Sulindac sulfide (cis-Sulindac sulfide) is a non-steroidal anti-inflammatory compound that has a high affinity for COX-1 and acts as an inhibitor in Ras activation of Raf-1. Sulindac sulfide is a non-competitive inhibitor of gamma-secretase with an IC50 value of 20.2 μM. It is an active metabolite of sulinic acid.

Dihydroergocristine mesylate (DHEC (mesylate))(DHEC mesylate) is the methanesulfonic acid salt of dihydroergocristine. It has been used as the for the symptomatic treatment of mental deterioration associated with cerebrovascular insufficiency and in peripheral vascular disease. Dihydroergocristine mesylate is a inhibitor of γ-secretase (GSI), , reduces the production of the Alzheimer's disease amyloid-β peptides, binds directly to γ-secretase and Nicastrin with equilibrium dissociation constants (Kd) of 25.7 nM and 9.8 μM, respectively[1]. It is also a component of ergoloid mesylate (codergocrine mesilate), a mixture of ergot alkaloid derivatives that is used as a vasodilator and has shown mild benefits in the treatment of vascular dementia. It has a role as a vasodilator agent, an alpha-adrenergic antagonist and a geroprotector. It contains a dihydroergocristine.

BMS-906024 (Osugacestat) is an orally available and selective inhibitor of γ-secretase, a small molecule Notch inhibitor.BMS-906024 has broad-spectrum antitumour activity against a variety of human cancer xenografts.BMS-906024 prevents the activation of all four Notch receptors, and is active against Notch1, -2, -3 and -4 receptors. BMS-906024 prevents the activation of all four Notch receptors, with IC50s of 1.6, 0.7, 3.4 and 2.9 nM for Notch1, -2, -3 and -4 receptors, respectively.

RO7185876 is a selective gamma secretase modulator, which can be used in the study of Alzheimer's disease.

JLK6 was a gamma-secretase inhibitor that does not interfere with Notch signalling

ELN318463 racemate (ELN 318463 racemate) is the racemate of ELN318463 which is an amyloid precursor protein (APP) selective γ-secretase inhibitor.

Aβ-IN-1 is a novel, potent and orally active γ-secretase modulator (GSM). Aβ-IN-1 potently reduced Aβ42 levels with an IC 50 value of 0.091 μM in cultured cells without inhibiting CYP3A4. Aβ-IN-1 shows a sustained pharmacokinetic profile.

BI-1408 is a modulator potent of γ secretase (IC50: 0.04 μM for Aβ42).

YO-01027 (DBZ) is a potent γ-secretase inhibitor.

Aβ42-IN-2 is a γ-secretase modulator. Aβ42-IN-2 has an IC 50 of 6.5 nM for Αβ 42. Aβ42-IN-2 can be used for the Alzheimer's disease research[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.

Crenigacestat (LY3039478) is an orally bioavailable Notch inhibitor with an IC50 of ~1 nM in most of the tumor cell lines tested. Crenigacestat effectively inhibits mutant Notch receptor activity. In a xenograft tumor model, Crenigacestat inhibited expression of Notch-regulated genes and N1ICD cleavage in the tumor microenvironment.

LY-411575 isomer 3 is a potent γ-secretase inhibitor. LY-411575 isomer 3 is an isomer of LY411575.

3,5-Bis(4-nitrophenoxy)benzoic acid (Compound W) is an inhibitor of γ-secretase. It also causes a decrease in the released levels of Aβ42 and notch-1 Aβ-like peptide 25 (Nβ25).

LY-411575 isomer 2 is a potent γ-secretase inhibitor. LY-411575 isomer 2 is an isomer of LY411575.

LY900009 is a small molecule inhibitor of Notch signalling via selective inhibition of the γ-secretase protein.

MRK003 is a γ-secretase inhibitor exhibits promising in vitro pre-clinical activity in multiple myeloma and non-Hodgkin's lymphoma. MRK003 treatment induced caspase-dependent apoptosis and inhibited proliferation of MM and NHL cell lines and patient cells. Examination of signaling events after treatment showed time-dependent decrease in levels of the notch intracellular domain, Hes1 and c-Myc. MRK003 downregulated cyclin D1, Bcl-Xl and Xiap levels in NHL cells and p21, Bcl-2 and Bcl-Xl in MM cells. In addition, MRK003 caused an upregulation of pAkt, indicating crosstalk with the PI3K/Akt pathway.

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

GSM-1 is a modulator of γ-Secretase.

Aβ42-IN-1, compound 1v, is a novel, potent and orally active γ-secretase modulator (GSM). Aβ42-IN-1 potently reduced Aβ42 levels with an IC 50 value of 0.091 μM in cultured cells without inhibiting CYP3A4. Aβ42-IN-1 shows a sustained pharmacokinetic profile.

RO-57-Bpyne is a γ-secretase modulator photoaffinity probe. It also can be exploited to reduce levels of pathogenic Aβ species. It acts by identifying distinct allosteric binding sites on presenilin.

BMS-932481 is a γ-secretase modulator.

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.

BMS 299897 is a sulfonamide γ-secretase inhibitor. It has an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP).

LY-411575 isomer 1 is a potent γ-secretase inhibitor. LY-411575 isomer 1 is an isomer of LY411575.

L458-BPyne is a γ-secretase modulator photoaffinity probe that acts by identifying distinct allosteric binding sites on presenilin. It also can be exploited to reduce levels of pathogenic Aβ species.

Potent γ-secretase inhibitor (IC50 values are 1.2 and 6.2 nM in whole cell and cell-free assays, respectively). Reduces Aβ in brain, CSF and plasma in mice and guinea pigs. Lanz et al (2010) Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014. J.Pharmacol.Exp.Ther. 334 269 PMID:20363853

Amyloid 17-42 (Aβ(17-42)), a significant component of diffuse plaques in Alzheimer's disease and cerebellar pre-amyloid in Down's syndrome, results from the alpha- and gamma-secretase cleavage of amyloid precursor protein (APP). It has the capability to trigger neuronal apoptosis through the Fas-like/caspase-8 activation pathway [1].

LY-411575 isomer 2 is an isomer of LY411575. LY411575 is a potent inhibitor of γ-secretase.