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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.
  • $34
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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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MK-0752
T2625471905-41-6
MK-0752, a γ-secretase inhibitor, reduces Aβ40 production(IC50=5 nM).
  • $52
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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).
  • $32
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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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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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Valproic Acid
T706499-66-1
Valproic Acid (2-Propylpentanoic Acid) is an HDAC inhibitor that suppresses HDAC1 activity and induces HDAC2 degradation, exhibiting oral bioavailability. Valproic Acid activates Notch1 signalling and inhibits the proliferation of small cell lung carcinoma cells, making it applicable for research into epilepsy and bipolar disorder.
  • $50
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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.
  • $176 TargetMol
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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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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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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).
  • $44
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YO-01027
T6135209984-56-5In house
YO-01027 (DBZ) is a potent γ-secretase inhibitor.
  • $30
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5β-Cholanic acid
T88859546-18-9
5β-Cholanic acid (5beta-Cholanic acid) is a potent γ-secretase modulator used in Alzheimer's disease research.
  • $37
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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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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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Prednisone acetate
T8396125-10-0
Prednisone acetate (Prednisone 21-acetate) is a glucocorticoid receptor agonist with immunomodulating properties and anti-inflammatory.
  • $30
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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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Withanolide A
TN230932911-62-9
Withanolide A extends the lifespan in human EGFR-driven cancerous Caenorhabditis elegans.
  • $99
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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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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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Divalproex Sodium
T647476584-70-8
Divalproex Sodium (Valproate semisodium) binds to and inhibits gamma-aminobutyric acid (GABA) transaminase and its anticonvulsant activity may be exerted by increasing brain concentration of GABA and by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. It also is an HDAC inhibitor, Comprised of sodium valproate and valproic acid with anticonvulsant and antiepileptic activities. Divalproex may also work by suppressing repetitive neuronal firing through the inhibition of voltage-sensitive sodium channels.
  • $33
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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].
  • $35
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Brontictuzumab
T767851447814-75-6
Brontictuzumab (OMP 52M5) is a monoclonal antibody that targets Notch1 and inhibits activation of the pathway. It has antitumor activity, inhibits tumor cell proliferation, and can be used in the study of leukemias and lymphomas.
  • $297
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