2. Signaling Pathways
  3. Neuronal Signaling
    Stem Cell/Wnt
  4. γ-secretase

γ-secretase

Gamma secretase

γ-secretase

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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).

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-120789
    PF-06648671
    		Modulator 99.25%
    PF-06648671 is a novel, brain-penetrable, and orally active γ-secretase modulator (GSM). PF-06648671 reduces Aβ42 and Aβ40, with concomitant increases in Aβ37 and Aβ38 in vitro. PF-06648671 is used for the study of Alzheimer’s disease.
    PF-06648671
  • HY-100604
    JNJ-40418677
    		Modulator 99.48%
    JNJ-40418677 is an orally active modulator of γ-secretase, can cross the blood-brain barrier. JNJ-40418677 inhibits Aβ42 and NS2B-NS3 protease, with IC50s of 200 nM and 3.9 μM, respectively. JNJ-40418677 displays good biological tolerance, can be use for Alzheimer’s disease research.
    JNJ-40418677
  • HY-B1786A
    (E/Z)-Sulindac sulfide
    		Modulator 99.88%
    (E/Z)-Sulindac sulfide is a potent γ-secretase modulator (GSM). (E/Z)-Sulindac sulfide selectively reduces Aβ42 production in favor of shorter Aβ species. (E/Z)-Sulindac sulfide can be used for researching Alzheimer’s disease.
    (E/Z)-Sulindac sulfide
  • HY-50883
    BMS 299897
    		Inhibitor 99.64%
    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).
    BMS 299897
  • HY-14175
    Begacestat
    		99.05%
    Begacestat (GSI-953) is a selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase (IC50Aβ40=15 nM) for the treatment of Alzheimer's disease.
    Begacestat
  • HY-B1786
    Sulindac sulfide
    		Inhibitor 98.10%
    Sulindac sulfide is a noncompetitive γ-secretase inhibitor, with an IC50 of 20.2 μM for γ42-secretase activity.
    Sulindac sulfide
  • HY-P4295
    Z-Phe-Ala-diazomethylketone
    		Inhibitor 98.06%
    Z-Phe-Ala-diazomethylketone binds directly to Aβ42 monomers and small oligomers. Z-Phe-Ala-diazomethylketone inhibits the formation of Aβ42 dodecamers and inhibits Aβ42 fibril formation in the solution. Z-Phe-Ala-diazomethylketone has the potential for neurodegenerative disorders research.
    Z-Phe-Ala-diazomethylketone
  • HY-111360
    SPL-707
    		Inhibitor 99.64%
    SPL-707 is an orally active, selective signal peptide peptidase-like 2a (SPPL2a) inhibitor with an IC50 of 77 nM for hSPPL2a. SPL-707 inhibits γ-secretase (IC50=6.1 μM) and SPP (IC50=3.7 μM). SPL-707 has the potential for autoimmune diseases research by targeting B cells and dendritic cells.
    SPL-707
  • HY-16632
    ELND 006
    		Inhibitor 99.7%
    ELND 006 (Compound 30) is a metabolically stable γ-secretase inhibitor designed to selectively inhibit amyloid beta (Aβ) generation while sparing Notch signaling. It was developed through a synthetic strategy emphasizing diversity and chirality. ELND 006, along with its analog ELND007 (Compound 34), progressed into human clinical trials. In preclinical studies, both compounds demonstrated effective reduction of Aβ levels in vitro and in vivo. Comparisons with other γ-secretase inhibitors like Semagacestat, Begacestat, and Avagacestat underscored their potency and specificity in lowering Aβ levels in cerebrospinal fluid (CSF) of healthy human volunteers, suggesting potential therapeutic efficacy in Alzheimer's disease.
    ELND 006
  • HY-W015515
    L-Citronellol
    		Inhibitor 99.92%
    L-Citronellol ((S)-3,7-Dimethyloct-6-en-1-ol) is a natural product with anti-allergic and neuroprotective effects. L-Citronellol inhibits mast cell activation and the release of inflammatory factors by inhibiting the ERK pathway. L-Citronellol inhibits BACE1/PSEN1 and AChE, reduces TNF-α expression and lipid peroxidation, demonstrating the potential of multi-target anti-Alzheimer's disease (AD).
    L-Citronellol
  • HY-145343
    RO7185876
    		Modulator 99.9%
    RO7185876 is a potent and selective gamma secretase modulator as a potential research for Alzheimer's disease.
    RO7185876
  • HY-171347
    gamma-secretase modulator 6
    		Modulator 99.68%
    gamma-secretase modulator 6 (Example 50) is a gamma-secretase modulator. gamma-secretase modulator 6 inhibits Aβ42 secretion in HEK cell line stably expressing APP (Aβ amyloid precursor protein) (pIC50: 8.1). gamma-secretase modulator 6 can be used for research of Alzheimer's disease.
    gamma-secretase modulator 6
  • HY-108714
    NGP555
    		Modulator 98.77%
    NGP555 is a γ-secretase modulator. NGP555 Lowers the Amyloid Biomarker Aβ42.
    NGP555
  • HY-115726
    FRM-024
    		Modulator 99.45%
    FRM-024 is a central nervous system-penetrant, orally active γ-secretase modulator and Aβ42 lowering agent. FRM-024 is used for the research of familial Alzheimer's disease.
    FRM-024
  • HY-18614
    LY900009
    		Inhibitor 98.40%
    LY900009 is a potent and orally active, First-in-class inhibitor of Notch signaling via selective inhibition of the γ-secretase protein (GSI). LY900009 inhibits Notch signalling in tumor cell lines and endothelial cells (IC50=0.005-20 nM). LY900009 can be used for advanced cancer research.
    LY900009
  • HY-171348
    Amyloid-β-IN-2
    		Inhibitor 99.47%
    Amyloid-β-IN-2 (Compound EX.112) is a selective γ-secretase inhibitor. Amyloid-β-IN-2 inhibits Aβ42 secretion in H4 cells with an EC50 value of 226 nM. Amyloid-β-IN-2 is promising for research of Alzheimer's disease (AD) and other diseases related to Aβ deposition.
    Amyloid-β-IN-2
  • HY-171349
    Amyloid-β-IN-3
    		Inhibitor 99.50%
    Amyloid-β-IN-3 (EX.113) is a selective γ-secretase inhibitor. Amyloid-β-IN-3 inhibits Aβ42 secretion in H4 cells with an EC50 value of 148 nM. Amyloid-β-IN-3 regulates the γ-secretase catalytic activity to decrease Aβ42 production, thereby alleviating neurotoxicity caused by Aβ deposition. Amyloid-β-IN-3 is promising for research of Alzheimer's disease (AD).
    Amyloid-β-IN-3
  • HY-171444
    GSM III
    		Modulator 99.67%
    GSM III is a γ-Secretase complexe (GSEC) modulator. GSM III significantly regulates amyloid-β (Aβ) length at the extracellular interface between the protease (NCT, PSEN) and the substrate APPC99. GSM III can be used for Alzheimer's disease (AD) research.
    GSM III
  • HY-119165
    GSM-1
    		Modulator 98.41%
    GSM-1 is a potent γ-secretase modulator. GSM-1 directly targets the transmembrane domain (TMD) 1 of presenilin 1 (PS1).
    GSM-1
  • HY-100604A
    (R)-JNJ-40418677
    		Control 99.67%
    (R)-JNJ-40418677 is the R-enantiomer of JNJ-40418677 (HY-100604).
    (R)-JNJ-40418677
Cat. No. Product Name / Synonyms Application Reactivity