γ-secretase

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.

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.

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

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

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.

Aβ42-IN-2, a γ-secretase modulator with an IC50 of 6.5 nM for Αβ42, can be used for Alzheimer's disease research [1].

Nirogacestat (PF 03084014) is a specific γ-secretase inhibitor (IC50: 6.2 nM, in a cell-free assay).

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

γ-Secretase modulator 4 is a potent γ-secretase modulator that reduces Aβ42 levels with IC50s of 0.017 μM in mice and 0.014 μM in humans.

E2012 is a γ-secretase modulator (GSM). E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. E 2012 aims at Alzheimer's disease by reduction of amyloid β-42, and induces cataract following repeated doses in the rat.

MRK-560 is an effective and brain-penetrant inhibitor of γ-secretase.

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

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

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

γ-Secretase modulator 10 (GSM-10) is a novel compound that modulates γ-secretase activity.

HDAC6-IN-9 is an orally active and highly effective γ-secretase modulator that can significantly reduce the level of Aβ42 in mouse brain and can be used to study neurological diseases.

γ-Secretase modulator 12 (Compound 1a) is a selective compound that effectively reduces amyloid-β42 (Aβ42) levels with an IC50 of 0.39 μM, 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].

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.

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

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.

Cimigenoside, a constituent of Asclepias, is a γ-secretase inhibitor that inhibits the proliferation or metastasis of human breast cancer cells via the γ-secretase/Notch axis.

γ-Secretase Modulator 14, a γ-secretase modulator, shows potential for use in Alzheimer's disease (AD) research (WO2013010904A1; compound 42) [1].

Fosciclopirox (CPX-POM), the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration.

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, significantly reduced brain Aβ42 levels, showed no inhibitory effect on cytochrome p450 enzymes, and demonstrated excellent anti-cognitive deficits in AD model mice.