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Gamma-secretase

Gamma secretase is a multi-subunit protease complex, itself an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. The most well-known substrate of gamma secretase is amyloid precursor protein, a large integral membrane protein that, when cleaved by both gamma and beta secretase, produces a short 37-43[verification needed] amino acid peptide called amyloid beta whose abnormally folded fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Gamma secretase is also critical in the related processing of several other type I integral membrane proteins, such as Notch, ErbB4, E-cadherin, N-cadherin, ephrin-B2, or CD44.

  • DAPT
    T6202208255-80-5
    DAPT (LY-374973) is a γ-secretase inhibitor that inhibits total Aβ and Aβ42 (IC50=115/200 nM) and is orally active. DAPT is also a Notch inhibitor. DAPT induces cell differentiation, autophagy and apoptosis.
    • $53
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  • RO7185876
    T397022226038-71-5In house
    RO7185876 is a selective gamma secretase modulator, which can be used in the study of Alzheimer's disease.
    • $293 TargetMol
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  • γ-Secretase-IN-1
    T3521209986-17-4
    γ-Secretase-IN-1 is a potent γ-secretase inhibitor that displays partial antiproliferative activity on T-47D cells and inhibits β-amyloid(40), β-amyloid(42), and Notch γ-secretase cleavage.
    • $129
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  • γ-Secretase modulator 13
    T622631353570-40-7In house
    γ-Secretase modulator 13 is a γ-secretase modulator (GSMs) that inhibits the production of amyloid β-peptide Aβ42 and can be used to study Alzheimer's disease and tumors.
    • $293 TargetMol
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  • Crenigacestat
    T36331421438-81-4
    Crenigacestat (LY3039478) is an orally bioavailable Notch inhibitor with an IC50 of ~1 nM in most tumor cell lines tested. It effectively inhibits mutant Notch receptor activity and, in a xenograft tumor model, inhibits the expression of Notch-regulated genes and N1ICD cleavage in the tumor microenvironment.
    • $56
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  • Valproic Acid
    T706499-66-1
    Valproic Acid (2-Propylpentanoic Acid) is an HDAC inhibitor that inhibits HDAC1 activity, induces HDAC2 degradation, and is orally active. Valproic Acid can be used in epilepsy and bipolar disorder research.
    • $50
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  • BMS-906024
    T146801401066-79-2In house
    BMS-906024 (Osugacestat) is an orally available and selective inhibitor of γ-secretase, a small molecule Notch inhibitor.BMS-906024 has broad-spectrum antitumour activity against a variety of human cancer xenografts.BMS-906024 prevents the activation of all four Notch receptors, and is active against Notch1, -2, -3 and -4 receptors. BMS-906024 prevents the activation of all four Notch receptors, with IC50s of 1.6, 0.7, 3.4 and 2.9 nM for Notch1, -2, -3 and -4 receptors, respectively.
    • $565
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  • RBPJ Inhibitor-1
    T355662682114-39-0
    RBPJ Inhibitor-1 (RIN1), a compound that impedes the functional interaction between RBPJ and SHARP, effectively inhibits NOTCH-dependent tumor cell proliferation[1].
    • $34
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  • JI051
    T117182234281-75-3
    JI051 is an antitumor agent that interacts with the cancer-associated protein chaperone prohibitin 2 (PHB2) to induce cell cycle arrest by inhibiting the transcription of the Notch downstream effector gene, Hes1, and inhibits the proliferation of HEK293 cells and pancreatic cancer cells.
    • $58
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  • NGP555
    T162941304630-27-0
    NGP555 is a modulator of γ-secretase.
    • $71
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  • YO-01027
    T6135209984-56-5In house
    YO-01027 (DBZ) is a potent γ-secretase inhibitor.
    • $44
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  • MDR-1339
    TQ00261018946-38-7
    MDR-1339 (DWK-1339) is an orally active, blood-brain-barrier-permeable inhibitor of amyloid-β (Aβ) aggregation.
    • $54
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  • MRK-560
    T16133677772-84-8
    MRK-560 is an effective and brain-penetrant inhibitor of γ-secretase.
    • $35
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  • L-685458
    T6870292632-98-5
    L-685458 (L-685,458) is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.
    • $122
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  • Tangeretin
    T2842481-53-8
    Tangeretin (NSC-618905), a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models and was also selected as a Notch-1 inhibitor.
    • $47
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  • Jagged-1 (188-204) TFA(219127-21-6 free base)
    TP1293
    Jagged-1 (188-204) TFA(219127-21-6 free base) is a fragment of the JAG-1 protein. JAG-1 is Notch ligand, a peptide that is the most conspicuously expressed ligand in skin. JAG-1 induces epidermal maturation. Exposing submerged keratinocytes monolayers to JAG-1 with elevated calcium concentration produces stratification with loricrin expression and NF-alphaB activation.
    • $235
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  • LY-411575
    T6063209984-57-6
    LY-411575, a potent γ-secretase inhibitor, is with IC50 of 0.078 nM in the membrane and 0.082 nM in cell-based. It also suppresses Notch clevage with IC50 of 0.39 nM.
    • $38
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  • Valproic acid sodium salt
    T16021069-66-5
    Valproic acid sodium salt (Sodium Valproate) is the sodium salt form of valproic acid with anti-epileptic activity. Valproic acid sodium salt is converted into its active form, valproate ion, in blood. Although the mechanism of action remains to be elucidated, Valproic acid sodium salt increases concentrations of gamma-aminobutyric acid (GABA) in the brain, probably due to inhibition of the enzymes responsible for the catabolism of GABA. This potentiates the synaptic actions of GABA. Valproic acid sodium salt may also affect potassium channels, thereby creating a direct membrane-stabilizing effect.
    • $42
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  • Bruceine D
    TWS204521499-66-1
    1. Bruceine D from Brucea javanica, may have the potential to be used as a natural viricide, or a lead compound for new viricides. 2. Bruceine D inhibits the growth of three pancreatic cancer cell lines, i.e., PANC-1, SW199 and CAPAN-1; induces cytotoxicity in Capan-2 cells via the induction of cellular apoptosis involving the mitochondrial pathway.
    • $41
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  • Legumain inhibitor 1
    T399052361157-34-6
    Legumain inhibitor 1 is a highly potent and specific Legumain inhibitor with potential anticancer activity for cancer research.
    • $299
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  • Nirogacestat
    T69351290543-63-3
    Nirogacestat (PF 03084014) is a specific γ-secretase inhibitor (IC50: 6.2 nM, in a cell-free assay).
    • $34
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  • ELN318463 racemate
    T11178L851599-82-1In house
    ELN318463 racemate (ELN 318463 racemate) is the racemate of ELN318463 which is an amyloid precursor protein (APP) selective γ-secretase inhibitor.
    • $165
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  • FLI-06
    T3075313967-18-9
    FLI-06 is a Notch signaling inhibitor (EC50: 2.3 μM).
    • $30
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  • Itanapraced
    T2262749269-83-8
    Itanapraced (CHF5074), a γ-secretase modulator, reduces Aβ42/40 secretion (IC50: 3.6/18.4 μM).
    • $31
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  • Psoralidin
    T339918642-23-4
    Psoralidin inhibits Akt phosphorylation and phosphatidylinositol 3-kinase activation and transcriptionally. Psoralidin possesses anticancer and chemopreventive properties.
    • $57
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  • ZLDI-8
    T13410667880-38-8
    ZLDI-8 is an inhibitor of Notch activating/cleaving enzyme ADAM-17 and inhibits the cleavage of Notch protein.
    • $52
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  • CIA-1 (Free base)
    T71534L452087-38-6
    CIA-1 (Free base) is a nuclear receptor COUP-TFII inhibitor with IC50 values ranging from 1.2 μM to 7.6 μM in prostate cancer cell lines. CIA-1 (Free base) inhibits tumor growth in a mouse model of prostate cancer xenografts.
    • $52
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  • RO4929097
    T6274847925-91-1
    RO4929097 (RG-4733), a γ secretase inhibitor (IC50: 4 nM), inhibits cellular processing of Aβ40 and Notch (EC50: 14/5 nM).
    • $40
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  • PE859
    T40771402727-29-0
    PE859 is a potent inhibitor of the aggregation of both tau and Aβ.
    • $61
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  • Rovalpituzumab
    T766981613313-01-1
    Rovalpituzumab is a humanized monoclonal antibody targeting delta-like protein 3 (DLL3) and is utilized to synthesize antibody-active molecule conjugates (ADCs). It exhibits anticancer activity and is used in the treatment of small cell lung cancer (SCLC).
    • $178
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  • Carvacrol
    T4S1990499-75-2
    1. Carvacrol (O-Thymol) presents anxiolytic effects. 2. 5-Isopropyl-2-methylphenol presents antinociceptive activity. 3. Carvacrol presents antidepressant effects, seems to be dependent on its interaction with the dopaminergic system, but not with the serotonergic and noradrenergic systems.
    • $42
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  • E 2012
    T15184870843-42-8
    E2012 is a γ-secretase modulator (GSM). E2012 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.
    • $29
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  • CB-103
    T12246218457-67-1
    CB-103 is a orally active inhibitor of notch signaling pathway, with anti-tumor activity.
    • $39
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  • Ro 90-7501
    T16773293762-45-5In house
    Ro 90-7501 is an amyloid β42 (Aβ42) protofibrillar and TPR-dependent PP5 inhibitor, a novel radiosensitizer for cervical cancer cells, which inhibits ATM phosphorylation, promotes apoptosis, and induces cell-cycle arrest. Ro 90-7501 also exhibits antiviral activity and potential anticancer activity by inhibiting ATM phosphorylation and DNA repair, and by inhibiting HCMV.
    • $30
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  • Semagacestat
    T6125425386-60-3
    Semagacestat (LY450139) (LY450139) is a γ-secretase blocker for Aβ42 Aβ40 Aβ38 (IC50: 10.9 12.1 12.0 nM) and also inhibits Notch signaling (IC50: 14.1 nM).
    • $33
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  • Avagacestat
    T62491146699-66-2
    Avagacestat (BMS-708163) (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.
    • $57
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  • JLK6
    T2189062252-26-0
    JLK6 was a gamma-secretase inhibitor that does not interfere with Notch signalling
    • $78
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  • IMR-1A
    T3540331862-41-0
    IMR-1A is the metabolite of IMR-1 which is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 6 μMol/L.
    • $68
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  • MK-0752
    T2625471905-41-6
    MK-0752, a γ-secretase inhibitor, reduces Aβ40 production(IC50=5 nM).
    • $29
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  • Fosciclopirox
    T94221380539-06-9
    Fosciclopirox (CPX-POM), the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration.
    • $30
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  • Aβ-IN-1
    T632082766509-32-2In house
    Aβ-IN-1 is a novel, potent and orally active γ-secretase modulator (GSM). Aβ-IN-1 potently reduced Aβ42 levels with an IC 50 value of 0.091 μM in cultured cells without inhibiting CYP3A4. Aβ-IN-1 shows a sustained pharmacokinetic profile.
    • $350
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  • Gossypolone
    T319874547-72-2In house
    Gossypolone is is a proposed major metabolite of gossypol. Gossypolone reduces Notch Wnt signaling and induces apoptosis.
    • $195
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  • BI-1408
    T105322231075-94-6In house
    BI-1408 is a modulator potent of γ secretase (IC50: 0.04 μM for Aβ42).
    • $350
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  • Aβ42-IN-2
    T96411914989-80-2In house
    Aβ42-IN-2, a γ-secretase modulator with an IC50 of 6.5 nM for Αβ42, can be used for Alzheimer's disease research [1].
    • $58
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  • gamma-secretase modulator 1
    T113581172637-87-4In house
    gamma-secretase modulator 1 is a modulator of γ secretase and can be used in studies about the treatment of Alzheimer's disease.
    • $34
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  • Jagged-1 (188-204)
    TP1540219127-21-6
    Jagged-1 (188-204)is a fragment of the JAG-1 protein. JAG-1 is Notch ligand, a peptide that is the most conspicuously expressed ligand in skin. JAG-1 induces epidermal maturation. Exposing submerged keratinocytes monolayers to JAG-1 with elevated calcium concentration produces stratification with loricrin expression and NF-αB activation.
    • $134
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  • LY900009
    T9015209984-68-9
    LY900009 is a small molecule inhibitor of Notch signalling via selective inhibition of the γ-secretase protein.
    • $32
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  • IMR-1
    T6861310456-65-6
    IMR-1, a novel class of Notch inhibitors, targets transcriptional activation with an IC50 of 6 μMol L.
    • $30
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  • 3,5-Bis(4-nitrophenoxy)benzoic acid
    T22678173550-33-9
    3,5-Bis(4-nitrophenoxy)benzoic acid (Compound W) is a γ-secretase inhibitor that reduces the levels of released Aβ42 and notch-1 Aβ-like peptide 25 (Nβ25).
    • $29
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  • Cimigenoside
    T6S167627994-11-2
    Cimigenoside, a constituent of Asclepias, is a γ-secretase inhibitor that inhibits the proliferation or metastasis of human breast cancer cells via the γ-secretase Notch axis.
    • $31
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