1. Neuronal Signaling
    Stem Cell/Wnt
  2. γ-secretase

γ-secretase

γ-Secretase is a multimeric aspartyl protease that cleaves the membrane-spanning region of the β-carboxyl terminal fragment (βCTF) generated from β-amyloid precursor protein. γ-Secretase defines the generated molecular species of amyloid β-protein (Aβ), a critical molecule in the pathogenesis of Alzheimer's disease (AD).

γ-Secretase is composed of four subunits: Aph-1, nicastrin (Nct), Pen-2 and presenilin (PS), which is the catalytic subunit of the enzyme. Endoproteolysis of PS, which results in the formation of PS1-NTF (N-terminal fragment) and CTF (C-terminal fragment) heterodimer, is required for γ-secretase activation. γ-Secretase cleaves amyloid precursor protein (APP), Notch and many other substrates. Aberrant cleavage of APP contributes to the pathogenesis of AD and abnormal Notch signaling promotes tumor growth. γ-Secretase is a highly valued drug target in Alzheimer's disease and cancer. Multiple classes of small molecules that target γ-secretase have been developed, including both inhibitors (GSIs) and modulators (GSMs).

γ-secretase Related Products (44):

Cat. No. Product Name Effect Purity
  • HY-13027
    DAPT Inhibitor 99.93%
    DAPT (GSI-IX) is a potent and orally active γ-secretase inhibitor with IC50s of 115 nM and 200 nM for total amyloid-β (Aβ) and 42, respectively. DAPT inhibits the activation of Notch 1 signaling and induces cell differentiation. DAPT also induces autophagy and apoptosis. DAPT has neuroprotection activity and has the potential for autoimmune and lymphoproliferative diseases, degenerative disease and cancers treatment[1][2].
  • HY-11102
    RO4929097 Inhibitor 98.29%
    RO4929097 (RG-4733) is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively[1].
  • HY-13526
    YO-01027 Inhibitor
    YO-01027 (Dibenzazepine;DBZ) is a potent γ-secretase inhibitor with IC50 values of 2.92 and 2.64 nM for Notch and APPL cleavage, respectively.
  • HY-50752
    LY-411575 Inhibitor
    LY-411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), and also inhibits Notch S3 cleavage with IC50 of 0.39 nM.
  • HY-12449
    Crenigacestat Inhibitor
    Crenigacestat (LY3039478) is an orally active Notch and γ-secretase inhibitor, with an IC50 of 1 nM in most of the tumor cell lines tested[1][2][3][4].
  • HY-115726
    FRM-024 Modulator
    FRM-024 is a potent CNS-penetrant gamma secretase modulator for familial Alzheimer’s disease.
  • HY-109174
    Fosciclopirox Inhibitor
    Fosciclopirox suppresses growth of urothelial cancer by targeting the γ-secretase complex. Fosciclopirox selectively delivers the active metabolite, Ciclopirox (CPX), to the entire urinary tract[1][2]. Ciclopirox has anticancer activity in a number of solid and hematologic malignancies.
  • HY-103539
    3,5-Bis(4-nitrophenoxy)benzoic acid Inhibitor
    3,5-Bis(4-nitrophenoxy)benzoic acid is an inhibitor of γ-secretase. 3,5-Bis(4-nitrophenoxy)benzoic acid causes a decrease in the released levels of Aβ42 and notch-1 Aβ-like peptide 25 (Nβ25). 3,5-Bis(4-nitrophenoxy)benzoic acid, as a marker for fetal hypothyroidism, is a 3,3’-diiodothyronine sulfate (T2S) cross-reactive material in maternal serum[1].
  • HY-15185
    Nirogacestat Inhibitor 98.23%
    Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective γ-secretase inhibitor with an IC50 of 6.2 nM. Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers[1].
  • HY-14176
    Compound E Inhibitor 99.91%
    Compound E is a γ-secretase inhibitor. Compound E bloks β-amyloid(40), β-amyloid(42), and Notch γ-secretase cleavage with IC50s of 0.24, 0.37, 0.32 nM, respectively.
  • HY-10974
    MK-0752 Inhibitor
    MK-0752 is a potent, orally active and specific γ-secretase inhibitor, showing dose-dependent reduction of Aβ40 with an IC50 of 5 nM in human SH-SY5Y cells. MK-0752 crosses the blood-brain barrier. MK-0752 reduces newly generated CNS Aβ in vivo[1][2].
  • HY-10009
    Semagacestat Inhibitor 99.56%
    Semagacestat is a γ-secretase inhibitor, inhibits β-amyloid (Aβ42), Aβ38 and Aβ40 with IC50s of 10.9, 12 and 12.1 nM, respectively; also inhibits Notch signaling with IC50 of 14.1 nM. Semagacestat can be used for the research of alzheimer's disease[1].
  • HY-15670
    BMS-906024 Inhibitor 98.07%
    BMS-906024 is an orally active and selective γ-secretase (gamma secretase) inhibitor. BMS-906024 is a potent pan-Notch receptors inhibitor with IC50s of 1.6 nM, 0.7 nM, 3.4 nM, and 2.9 nM for Notch1, -2, -3, and -4 receptors, respectively. BMS-906024 demonstrates broad-spectrum antineoplastic activity[1][2].
  • HY-19369
    L-685458 Inhibitor 99.33%
    L-685458 is a potent transition state analog (TSA) γ-secretase inhibitor (GSI). L-685458 inhibits amyloid β-protein precursor γ-secretase activity with IC50 of 17 nM, shows greater than 50-100-fold selectivity over other aspartyl proteases tested. L685458 inhibits γ-secretase-mediated cleavage of APP-C99 and Notch-100 with IC50s of 301.3 nM and 351.3 nM, respectively. L-685458 can be used for the research of alzheimer’s disease (AD) and cancers[1][2].
  • HY-10016
    E 2012 Modulator
    E 2012 is a potent gamma (γ) secretase modulator without affecting Notch processing. E 2012 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[1].
  • HY-50845
    Avagacestat Inhibitor
    Avagacestat (BMS-708163) is a potent inhibitor of γ-secretase, with IC50s of 0.27 nM and 0.30 nM for Aβ42 and Aβ40 inhibition; Avagacestat (BMS-708163) also inhibits NICD (Notch IntraCellular Domain) with IC50 of 0.84 nM and shows weak inhibition of CYP2C19, with IC50 of 20 μM. Avagacestat can be used for Alzheimer disease research.
  • HY-108714
    NGP555 Modulator 98.09%
    NGP555 is a γ-secretase modulator.
  • HY-50883
    BMS 299897 Inhibitor 98.96%
    BMS 299897 is a sulfonamide γ-secretase inhibitor with an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP).
  • HY-14399
    Itanapraced Inhibitor
    Itanapraced (CHF5074) is a novel γ-secretase modulator, reduces Aβ42 and Aβ40 secretion, with an IC50 of 3.6 and 18.4 μM, respectively.
  • HY-14174
    MRK-560 Inhibitor
    MRK-560 is a potent, orally bioavailable and brain-penetrant γ-secretase inhibitor[1].