1. Signaling Pathways
  2. Neuronal Signaling
    Stem Cell/Wnt
  3. 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 (53):

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.
  • HY-11102
    RO4929097
    Inhibitor 98.89%
    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.
  • HY-50752
    LY-411575
    Inhibitor ≥98.0%
    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-13526
    YO-01027
    Inhibitor 99.94%
    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-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-145428
    BT-GSI
    Inhibitor
    BT-GSI is a γ-secretase inhibitor (GSI) and a bone-targeted Notch inhibitor. BT-GSI has dual anti-myeloma and anti-resorptive properties, which can be used for the research of multiple myeloma and associated bone disease. BT-GSI inhibits tumor growth and osteolytic disease progression.
  • HY-B1786A
    (E/Z)-Sulindac sulfide
    Modulator
    (E/Z)-Sulindac sulfide is a potent γ-secretase modulator (GSM). (E/Z)-Sulindac sulfide selectively reduces Aβ42 production in favor of shorter species. (E/Z)-Sulindac sulfide can be used for researching Alzheimer’s disease.
  • HY-147720
    γ-Secretase modulator 11
    5-{8-[(3,4'- difluoro [1,1'- biphenyl]-4-yl) methoxy] - 2-methylimidazo [1,2-a] pyridin-3-yl}-n-methylpyridin-2-formamide (1o) showed high potency in vitro and brain exposure, inducing brain a β 42 levels were significantly reduced and showed undetectable inhibition of cytochrome P450 enzymes. In addition, compound 1o showed excellent anti cognitive deficit effect in AD model mice.
  • HY-12449
    Crenigacestat
    Inhibitor 98.33%
    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.
  • HY-15185
    Nirogacestat
    Inhibitor 98.76%
    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.
  • HY-10974
    MK-0752
    Inhibitor 98.76%
    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.
  • 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.
  • 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.
  • 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.
  • HY-50845
    Avagacestat
    Inhibitor 98.28%
    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-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.
  • HY-B1786
    Sulindac sulfide
    Inhibitor 99.07%
    Sulindac sulfide is a noncompetitive γ-secretase inhibitor, with an IC50 of 20.2 μM for γ42-secretase activity.
  • HY-50883
    BMS 299897
    Inhibitor 99.24%
    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-14174
    MRK-560
    Inhibitor ≥99.0%
    MRK-560 is an orally active, brain barrier-penetrating γ-Secretase inhibitor, can potently reduces Aβ peptide in rat brain and cerebrospinal fluid. MRK-560 also decreases mutant NOTCH1 processing by selectively inhibiting PSEN1. MRK-560 can be used in studies of Alzheimer's disease and T-cell acute lymphoblastic leukaemia (T-ALL).
  • HY-108714
    NGP555
    Modulator 98.09%
    NGP555 is a γ-secretase modulator.