AZ1136
AZ1136 is a γ-secretase modulator that regulates amyloid-β (Aβ) production without reducing total Aβ generation. AZ1136 also modulates γ-secretase-mediated Notch S4 cleavage, but does not inhibit NICD formation. AZ1136 can be used in studies related to γ-secretase, APP processing and Alzheimer's disease.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- CAS No.: 1380508-60-0
- Formule: C24H21N5O3
- Masse moléculaire:427.46
-
Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Activité biologique
Description
In Vitro
AZ1136 (25 μM; 2 h) modulates γ-secretase-mediated APP processing in HEK/APPswe cell membranes, reduces the levels of Aβ42 and Aβ40, increases the levels of short-chain Aβ37 and Aβ38, alters specific short peptide cleavage products, and preferentially affects the turnover of Aβ42 without inhibiting the overall activity of γ-secretase[1].
AZ1136 modulates γ-secretase-mediated Aβ production in HEK/APPswe cells, potently reduces the levels of amyloidogenic Aβ42 (IC50 = 990 nM) and Aβ40 (IC50 = 1400 nM), while increasing the shorter, less amyloidogenic Aβ37 and Aβ39, without altering total Aβ levels[2].
AZ1136 (25 μM; 16 h) reduces Aβ40 and Aβ42 by 2.3-fold and 8.3-fold, respectively, increases Aβ37 and Aβ39 by 3.5-fold and 2.1-fold, respectively, in HEK/APPswe cells, while Aβ38 remains unaffected[2].
AZ1136 (5 h) modulates γ-secretase-mediated APP processing in HEK/APPswe cells, reduces the levels of Aβ42 (IC50 990 nM) and Aβ40 (IC50 1400 nM) (with higher potency against Aβ42), and increases the shorter Aβ37 and Aβ39 peptides, without altering total Aβ levels or inducing cytotoxicity[3].
AZ1136 (0-5 μM; 5 h) competes with AZ4800 for binding to a common molecular target in HEK/APPswe cells, indicating that both belong to the same class of second-generation γ-secretase modulators[3].
AZ1136 (2 h) retains Aβ-modulating activity in both HEK/APPswe-derived total membranes (TM) and carbonate-extracted membranes (CEM), significantly inhibiting Aβ42 and increasing Aβ37; a slight increase in Aβ38 is also observed in this cell-free membrane assay[3].
AZ1136 (25 μM; 24 h) modulates γ-secretase-mediated Notch N peptide production in HEK/FLAG-Notch1-ΔE cells, reducing F-N24 and F-N25 by 2.0-fold and 2.6-fold, respectively, and increasing F-N18 by 1.7-fold[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Chemical Information
-
CAS No. 1380508-60-0
-
Masse moléculaire 427.46
-
Formule C24H21N5O3
-
SMILES
O=C1C2=CN=C(OC3=CC=C(C4=CN=CO4)C=C3)N=C2N(C)CC(C5=CC=CC=C5)N1C
-
Livraison
Room temperature in continental US; may vary elsewhere.
-
Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
-
Notch Pathway Solutions
The Notch pathway is a contact-dependent signaling pathway that controls cell-fate decisions, differentiation, proliferation, and tissue patterning through interactions between membrane-bound Notch receptors and membrane-bound ligands on neighboring cells. Canonical Notch signaling is activated when ligand engagement triggers proteolytic release of the Notch intracellular domain, which enters the nucleus and regulates transcription together with DNA-binding transcriptional complexes. In the canonical mechanism, ligand-dependent Notch activation leads to release of the intracellular Notch domain, and presenilin-dependent γ-secretase activity is required for production of the active intracellular signaling fragment. The released intracellular domain functions as a nuclear signal that converts Notch receptor activation at the membrane into transcriptional regulation of target programs such as HES/HEY-family genes and other context-dependent downstream targets. The literature links Notch p
-
Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
-
Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Pureté et documentation
Références
[2]. Wanngren J, et al. Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production. The Journal of biological chemistry. 2012 Sep 21;287(39):32640-50. [Content Brief]
[3]. Borgegard T, et al. First and second generation γ-secretase modulators (GSMs) modulate amyloid-β (Aβ) peptide production through different mechanisms. The Journal of biological chemistry. 2012 Apr 06;287(15):11810-9. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)