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 (65):

Cat. No. Product Name Effect Purity
  • HY-13027
    DAPT Inhibitor 99.91%
    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-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-15185
    Nirogacestat Inhibitor 98.40%
    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-50752
    LY-411575 Inhibitor 99.33%
    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-14176
    Compound E Inhibitor 99.95%
    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-148306
    γ-Secretase modulator 14 Modulator
    γ-Secretase modulator 14 is a γ-secretase modulator. γ-Secretase modulator 14 has the potenial for Alzheimer's disease (AD) research (WO2013010904A1; compound 42)[1].
  • HY-109174A
    Fosciclopirox disodium Inhibitor
    Fosciclopirox disodium suppresses growth of urothelial cancer by targeting the γ-secretase complex. Fosciclopirox disodium selectively delivers the active metabolite, Ciclopirox (HY-B0450), to the entire urinary tract. Ciclopirox has anticancer activity in a number of solid and hematologic malignancies[1][2].
  • HY-117957
    BMS-932481 Modulator
    BMS-932481 is an orally active modulator for γ-secretase, selectively reduce Aβ1-42 and Aβ1-40 production, with IC50s of 6.6 and 25.3 nM, respectively[1].
  • 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-103537
    (Rac)-BIIB042 Modulator
    (Rac)-BIIB042 (Compound 10) is an modulator of γ-Secretase. (Rac)-BIIB042 reduces Amyloid-β 42 level with an EC50 value of 0.39 µM. (Rac)-BIIB042 can be used for the study of Alzheimer's disease[1].
  • HY-50752B
    LY-411575 (isomer 2) 99.84%
    LY-411575 isomer 2 is an isomer of LY411575, which is a potent γ-secretase inhibitor.
  • HY-50754
    gamma-secretase modulator 2 Modulator 98.80%
    gamma-secretase modulator 2 is a potent and selective γ-secretase modulator for treatment of Alzheimer's disease IC50 value: Target: γ-secretase γ-secretase modulator is modulation of the action of γ-secretase so as to Selectively attenuate production of Aβ(1-42) and hence find use in treatment or prevention of diseases associated with deposition of Aβ in the brain.
  • HY-115726
    FRM-024 Modulator
    FRM-024 is a potent CNS-penetrant gamma secretase modulator for familial Alzheimer’s disease.
  • HY-10043
    gamma-secretase modulator 1 Modulator
    γ-secretase inhibitior-1 is a gamma-secretase modulator, γ-secretase inhibitior-1 is useful for Alzheimer's disease.
  • 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[1].
  • HY-145372
    γ-Secretase modulator 10 Modulator
    γ-Secretase modulator 10 is a novel γ-secretase modulator.
  • HY-145343
    RO7185876 Modulator
    RO7185876 is a potent and selective gamma secretase modulator as a potential research for Alzheimer's disease.
  • 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-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[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.