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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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  • 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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  • 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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  • 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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  • 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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  • 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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  • JLK6
    T2189062252-26-0
    JLK6 was a gamma-secretase inhibitor that does not interfere with Notch signalling
    • $133
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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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  • 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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  • 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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  • 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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  • 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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  • 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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  • YO-01027
    T6135209984-56-5In house
    YO-01027 (DBZ) is a potent γ-secretase inhibitor.
    • $44
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  • Aβ42-IN-2
    T96411914989-80-2In house
    Aβ42-IN-2 is a γ-secretase modulator. Aβ42-IN-2 has an IC 50 of 6.5 nM for Αβ 42. Aβ42-IN-2 can be used for the Alzheimer's disease research[1].
    • $58
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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 radiosensitiser for cervical cancer cells, which inhibits ATM phosphorylation, promotes apoptosis, and induces cell-cycle arrest.Ro 90-7501 exhibits antiviral activity and potential anticancer activity by inhibiting ATM phosphorylation and DNA repair, and by inhibiting HCMV.
    • $30
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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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  • 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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  • 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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  • 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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  • Crenigacestat
    T36331421438-81-4
    Crenigacestat (LY3039478) is an orally bioavailable Notch inhibitor with an IC50 of ~1 nM in most of the tumor cell lines tested. Crenigacestat effectively inhibits mutant Notch receptor activity. In a xenograft tumor model, Crenigacestat inhibited expression of Notch-regulated genes and N1ICD cleavage in the tumor microenvironment.
    • $56
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    TargetMol | Citations Cited
  • 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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  • Demcizumab
    T767881243262-17-0
    Demcizumab (OMP 21M18) is an anti-DLL4 monoclonal antibody. Demcizumab is a potent Notch pathway inhibitor. Demcizumab is effective in multiple cancer models, both alone and in combination with chemotherapy agents.
    • $372
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  • 3,5-Bis(4-nitrophenoxy)benzoic acid
    T22678173550-33-9
    3,5-Bis(4-nitrophenoxy)benzoic acid (Compound W) is an inhibitor of γ-secretase. It also causes a decrease in the released levels of Aβ42 and notch-1 Aβ-like peptide 25 (Nβ25).
    • $50
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  • Rovalpituzumab
    T766981613313-01-1
    Rovalpituzumab is a humanized monoclonal antibody targeting delta-like protein 3 (DLL3). Rovalpituzumab can be used to synthesize antibody-active molecule conjugates (ADCs). Rovalpituzumab has anticancer activity and is used to treat small cell lung cancer (SCLC).
    • $178
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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.
    • $54
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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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  • MK-0752
    T2625471905-41-6
    MK-0752, a γ-secretase inhibitor, reduces Aβ40 production(IC50=5 nM).
    • $52
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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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  • 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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  • 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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  • PE859
    T40771402727-29-0
    PE859 is a potent inhibitor of both tau and Aβ aggregation.
    • $119
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  • IMR-1
    T6861310456-65-6
    IMR-1 is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 6 μMol/L.
    • $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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  • BMS-983970
    T146831584713-87-0
    BMS-983970 is an oral inhibitor of pan-Notch, and for the treatment of multiplecancers.
    • $198
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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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  • 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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  • 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).
    • $34
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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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  • 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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  • CIA-1 hcl(452087-38-6 Free base)
    T715341049691-47-5
    CIA-1 inhibits the nuclear receptor COUP-TFII, with IC50s ranging from 1.2 μM to 7.6 μM in prostate cancer cell lines.CIA-1 inhibits the growth of a variety of prostate cancer cell lines in vitro and inhibits COUP-TFII activity to regulate its target genes.CIA-1 in vivo exhibits tumor growth inhibitory effects in a mouse model of prostate cancer xenografts. inhibitory effect on tumor growth in a xenograft mouse model of prostate cancer in vivo.
    • $393
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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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  • 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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  • 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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  • 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.
    • $34
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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.
    • $52
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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.
    • $116
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  • Aftin-4
    T4364866893-90-5
    Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4(Aftin4) increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4(Aftin4) can thus be used to induce a rapid, acute Alzheimer's disease-like toxicity in the rodent brain.
    • $41
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