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Z-Ile-Leu-aldehyde (Synonyms: Z-IL-CHO; GSI-XII; γ-Secretase inhibitor XII)

Catalog No.GC15896

potent gamma-Secretase inhibitor

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Z-Ile-Leu-aldehyde Chemical Structure

Cas No.: 161710-10-7

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10mM (in 1mL DMSO)
$270.00
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5mg
$255.00
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10mg
$335.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

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Background

Z-Ile-Leu-aldehyde (gamma-Secretase inhibitor XII /GSI XII, Z-IL-CHO) is a potent gamma-Secretase inhibitor and Notch signaling inhibitor.

Notch signaling impinges on many cellular processes, including cell proliferation, differentiation, apoptosis, and maintenance of stem cells. It is also involved in many developmental systems, including neurogenesis, angiogenesis, hematopoiesis, and myogenesis. Deregulation of Notch signaling leads to developmental syndromes and cancer [3]. In order to transmit a signal, Notch receptors undergo a series of proteolytic cleavages after binding their cognate ligands of the Delta-like and Jagged family. γ-Secretase is a large protease complex that cleaves the membrane-bound form of Notch and releases the intracellular domain of the Notch receptor. This step in Notch signaling is pivotal in the activation of this signaling cascade [1] [2].

In vitro: GSI XII (10~15 µM) blocked the Notch signaling, reduced cell viability and induced apoptosis in MOPC315.BM murine multiple myeloma cells in vitro. GSI XII (10 µM) impaired murine osteoclast differentiation of receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 murine monocyte/macrophage cell line [1]. GSI XII (8 μM ~ 15 μM) potently triggered an apoptotic response through inhibition of Notch activity in the breast cancer cells. GSI XII also targets mammary cancer stem-like cells because it dramatically prevented in vitro mammosphere formation [3].

In vivo: Notch inhibition through GSI XII (intraperitoneal injection, 10 mg/kg) reduced myeloma-specific paraprotein levels, bone loss and diminished osteolytic lesions in the MOPC315.BM mice model[1]. Notch inhibition using GSI XII (intraperitoneal injection, 5 mg/kg) blocked embryonal rhabdomyosarcoma tumorigenesis in mice[2].

ex vivo: A model of 3D culture of human breast cancer tissues was developed to study a series of 30 consecutive primary tumors from patients with untreated breast cancer for their sensitivity to the Notch inhibitor GSI XII (15 μM). The results indicated that 24 tumors are sensitive to apoptosis induction by GSIXII.

References:
[1].  Schwarzer R, Nickel N, Godau J, et al. Notch pathway inhibition controls myeloma bone disease in the murine MOPC315. BM model[J]. Blood cancer journal, 2014, 4(6): e217.
[2].  Belyea B C, Naini S, Bentley R C, et al. Inhibition of the Notch-Hey1 axis blocks embryonal rhabdomyosarcoma tumorigenesis[J]. Clinical Cancer Research, 2011, 17(23): 7324-7336.
[3].  Séveno C, Loussouarn D, Bréchet S, et al. γ-Secretase inhibition promotes cell death, Noxa upregulation, and sensitization to BH3 mimetic ABT-737 in human breast cancer cells[J]. Breast Cancer Research, 2012, 14(3): R96.

Chemical Properties

Cas No. 161710-10-7 SDF
Synonyms Z-IL-CHO; GSI-XII; γ-Secretase inhibitor XII
Chemical Name benzyl ((2R,3R)-3-methyl-1-(((R)-4-methyl-1-oxopentan-2-yl)amino)-1-oxopentan-2-yl)carbamate
Canonical SMILES O=C(N[C@@H](C(N[C@@H](C=O)CC(C)C)=O)[C@@H](CC)C)OCC1=CC=CC=C1
Formula C20H30N2O4 M.Wt 362.46
Solubility ≥ 10.8mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.7589 mL 13.7946 mL 27.5893 mL
5 mM 0.5518 mL 2.7589 mL 5.5179 mL
10 mM 0.2759 mL 1.3795 mL 2.7589 mL
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