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

γ-secretase

Gamma 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).

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-15211
    MRK 003
    Inhibitor
    MRK 003 is a potent, selective and orally active γ-secretase inhibitor. MRK 003 reduce brain Aβ production in vivo. MRK 003 induces caspase-dependent apoptosis and inhibits tumor cell proliferation in vivo and in vitro.
    MRK 003
  • HY-156011
    PSEN1-IN-1
    Inhibitor
    PSEN1-IN-1 (Compound (+)-13b) is a PSEN1 inhibitor. PSEN1-IN-1 inhibits PSEN1-APH1A and PSEN1-APH1B complex with IC50s of 19 and 5.5 nM. PSEN1-IN-1 can be used for Alzheimer's disease research.
    PSEN1-IN-1
  • 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.
    BMS-932481
  • HY-B1786S
    Sulindac sulfide-d3
    Inhibitor
    Sulindac sulfide-d3 is deuterium labeled Sulindac sulfide. Sulindac sulfide is a noncompetitive γ-secretase inhibitor, with an IC50 of 20.2 μM for γ42-secretase activity.
    Sulindac sulfide-d<sub>3</sub>
  • HY-164451
    GSI-18
    Inhibitor
    GSI-18 is a γ-secretase inhibitor with anticancer activity. GSI-18 inhibits the attachment-free growth of pancreatic cancer cells by inhibiting Notch signaling.
    GSI-18
  • HY-16633
    ELND 007
    Inhibitor
    ELND 007 (Compound 34) is a metabolically stable γ-secretase inhibitor designed to selectively inhibit amyloid beta (Aβ) generation while minimizing Notch inhibition. Developed alongside ELND 006 (Compound 30), it underwent human clinical trials following a synthetic strategy emphasizing diversity and chirality. In preclinical studies, ELND 007 showed promising in vitro and in vivo characteristics, effectively reducing Aβ levels. Comparative studies with other γ-secretase inhibitors like Semagacestat, Begacestat, and Avagacestat highlighted its efficacy in lowering Aβ production, particularly demonstrated by reduced Aβ levels in the cerebrospinal fluid (CSF) of healthy human volunteers, suggesting potential therapeutic benefit for Alzheimer's disease.
    ELND 007
  • HY-14176G
    Compound E (GMP)
    Inhibitor
    Compound E (GMP) is a GMP-grade Compound E (HY-14176). GMP-grade small molecules can be used as adjuvant reagents in cell therapy. Compound E is a γ-secretase inhibitor. Compound E inhibits β-amyloid(40), β-amyloid(42), and Notch γ-secretase cleavage with IC50 values ​​of 0.24, 0.37, and 0.32 nM, respectively.
    Compound E (GMP)
  • HY-50884
    BMS 433796
    Inhibitor
    BMS 433796 is a γ-secretase inhibitor with lowering activity in a transgenic mouse model of Alzheimer's disease.
    BMS 433796
  • HY-117381
    γ-secretase-IN-2
    Inhibitor
    γ-secretase-IN-2 (Compound 36) is an inhibitor for γ-secretase, with an IC50 of 0.07 nM.
    γ-secretase-IN-2
  • HY-159836
    Nivegacetor
    Modulator
    Nivegacetor is a potent γ-secretase modulator.
    Nivegacetor
  • HY-158012
    LY3056480
    Inhibitor
    LY3056480 is a gamma-secretase inhibitor (GSI) that inhibits Notch signaling. LY3056480 improves mild to moderate sensorineural hearing loss and is safe and tolerable. Intratympanic administration of LY3056480 induces hair cell regeneration and partial hearing recovery in mammals.
    LY3056480
  • HY-163885
    SSZ
    Inhibitor
    SSZ is a multi-target inhibitor, which targets multiple pathological mechanisms of Alzheimer's disease (AD). SSZ targets acetylcholinesterase, butyrylcholinesterase, β-site amyloid precursor protein cleavage enzyme 1 (BACE1), and γ-secretase. SSZ ameliorates Alzheimer’s diseases and exhibits neuroprotective effect in mice.
    SSZ
  • HY-146151
    γ-Secretase modulator 12
    Modulator
    γ-Secretase modulator 12 (Compound 1a) is a γ-secretase modulator that can selectively decrease amyloid-β42 (Aβ42) levels (IC50 of 0.39 µM). γ-Secretase modulator 12 can be used for Alzheimer’s disease research. γ-Secretase modulator 12 has a good brain/plasma ratio (Kp, brain = 0.72) in mice.
    γ-Secretase modulator 12
  • HY-147720A
    γ-Secretase modulator 11 hydrochloride
    Modulator
    γ-Secretase modulator 11 hydrochloride (compound 1o) is a potent and orally active γ-secretase modulator with an IC50 of 0.029 µM. γ-Secretase modulator 11 hydrochloride induces a robust reduction in brain Aβ42 levels. γ-Secretase modulator 11 hydrochloride rescues cognitive deficits exhibited by AD model mice. γ-Secretase modulator 11 hydrochloride has the potential for the research of alzheimer's disease.
    γ-Secretase modulator 11 hydrochloride
  • HY-139052
    III-31-C
    Inhibitor
    III-31-C is a (hydroxyethyl)urea γ-secretase inhibitor. III-31-C inhibits Aऔ production with an IC50 of 10 nM in the cell-free γ-secretase assay and 200 nM in APP-transfected cells. III-31-C can be used in Alzheimer's disease research.
    III-31-C
  • HY-19550
    PF-06442609
    Modulator
    PF-06442609 is an orally active γ secretase modulator, with an IC50 of 6 nM for Aβ42. PF-06442609 possesses brain good penetration.
    PF-06442609
  • HY-B1786R
    Sulindac sulfide (Standard)
    Inhibitor
    Sulindac sulfide (Standard) is the analytical standard of Sulindac sulfide. This product is intended for research and analytical applications. Sulindac sulfide is a noncompetitive γ-secretase inhibitor, with an IC50 of 20.2 μM for γ42-secretase activity.
    Sulindac sulfide (Standard)
  • HY-50752B
    LY-411575 (isomer 2)
    99.84%
    LY-411575 isomer 2 is an isomer of LY411575, which is a potent γ-secretase inhibitor.
    LY-411575 (isomer 2)
  • HY-50752A
    LY-411575 (isomer 1)
    99.51%
    LY-411575 isomer 1 is an isomer of LY411575, which is a potent γ-secretase inhibitor.
    LY-411575 (isomer 1)
  • HY-112282
    BI-1408
    Modulator
    BI-1408 is a potent γ secretase modulator with an IC50 of 0.04 μM for 42.
    BI-1408
Cat. No. Product Name / Synonyms Application Reactivity