Z-LLNle-CHO
Based on 1 Customer Validation
Z-LLNle-CHO (Z-Leu-Leu-Nle-CHO) is a γ-secretase inhibitor I. Z-LLNle-CHO induces caspase and ROS-dependent apoptosis by blocking the Akt-mediated pro-survival pathway. Z-LLNle-CHO can be used in cancer research, such as breast cancer and leukaemia.
For research use only. We do not sell to patients.
- Purity : 97.18%
- CAS No.: 133407-83-7
- Formula: C26H41N3O5
- Molecular Weight:475.62
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Storage:
Sealed storage, away from moisture.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Biological Activity
Description
In Vitro
Z-LLNle-CHO (0-5 μM or 0-3 μM; 72 h) results in a dose-dependent decrease in cell viability/proliferation in six breast cancer cell lines[1].
Z-LLNle-CHO shows proteasome inhibitory activity, which contributes to cytotoxicity to MCF-7 cells[1].
Z-LLNle-CHO blocks Akt-mediated pro-survival pathways and induces caspase- and ROS-dependent cell apoptosis in Nalm6 and 697 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:MCF-7, BT474, T47D, MDA-MB-231, SKBR3, and MDA-MB-468 cells
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Concentration:0-5 µM (for MCF-7); 0-3 µM
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Incubation Time:72 h
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Result:Inhibited MCF-7, BT474, T47D, MDA-MB-231, SKBR3, and MDA-MB-468 cells with ED50 values of 3.25, 2.5, 2.4, 1.8, 1.6, and 1.4 μM, respectively.
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Cell Line:Precursor-B ALL cells
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Concentration:0-2.5 µM
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Incubation Time:18-24 h
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Result:Induced cell apoptosis.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female SCID/NOD mice (6-8-week-old; precursor-B ALL xenograft model)[2].
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Dosage:5 mg/kg
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Administration:Subcutaneous injection; single daily for 12 days
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Result:Delayed or prevented engraftment of B-lymphoblasts in 50% of the animals comprising the experimental group.
Chemical Information
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CAS No. 133407-83-7
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Appearance Solid
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Molecular Weight 475.62
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Formula C26H41N3O5
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Color White to off-white
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Synonyms
Z-Leu-Leu-Nle-CHO; GSII
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Sealed storage, away from moisture
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (210.25 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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ROS/oxidative-stress fluorescent staining
ROS/oxidative-stress fluorescent staining uses cell-permeant fluorogenic probes that become fluorescent after oxidation inside cells or tissues; commonly used examples include DCFH-DA/DCFDA for broad cellular oxidant detection, DHE for superoxide-related signal detection, MitoSOX for mitochondrial superoxide-related signal detection, and CellROX probes for oxidative-stress-associated fluorescence readouts. The assay detects probe oxidation rather than a single ROS species unless the probe and analysis method have been chemically validated for that species. DCFH-DA enters cells, is deacetylated by intracellular esterases to DCFH, and produces fluorescent DCF after oxidation, so the readout is used as an operational measure of total cellular oxidative stress rather than a species-specific ROS measurement. DHE and MitoSOX can report superoxide-related oxidation, but red fluorescence alone can include non-specific ethidium-like oxidation products; HPLC or optimized spectral approaches are
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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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
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Han J, et al. The cytotoxicity of gamma-secretase inhibitor I to breast cancer cells is mediated by proteasome inhibition, not by gamma-secretase inhibition. Breast Cancer Res. 2009;11(4):R57. [Content Brief]
[2]. Meng X, et al. GSI-I (Z-LLNle-CHO) inhibits γ-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia. Leukemia. 2011 Jul;25(7):1135-46. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1025 mL | 10.5126 mL | 21.0252 mL | 52.5630 mL |
| 5 mM | 0.4205 mL | 2.1025 mL | 4.2050 mL | 10.5126 mL | |
| 10 mM | 0.2103 mL | 1.0513 mL | 2.1025 mL | 5.2563 mL | |
| 15 mM | 0.1402 mL | 0.7008 mL | 1.4017 mL | 3.5042 mL | |
| 20 mM | 0.1051 mL | 0.5256 mL | 1.0513 mL | 2.6281 mL | |
| 25 mM | 0.0841 mL | 0.4205 mL | 0.8410 mL | 2.1025 mL | |
| 30 mM | 0.0701 mL | 0.3504 mL | 0.7008 mL | 1.7521 mL | |
| 40 mM | 0.0526 mL | 0.2628 mL | 0.5256 mL | 1.3141 mL | |
| 50 mM | 0.0421 mL | 0.2103 mL | 0.4205 mL | 1.0513 mL | |
| 60 mM | 0.0350 mL | 0.1752 mL | 0.3504 mL | 0.8760 mL | |
| 80 mM | 0.0263 mL | 0.1314 mL | 0.2628 mL | 0.6570 mL | |
| 100 mM | 0.0210 mL | 0.1051 mL | 0.2103 mL | 0.5256 mL |