ZSNI-21
ZSNI-21 is a ADAM17/HDAC2 inhibitor with ADAM17 IC50 0.939 μM and HDAC2 IC50 0.844 μM. ZSNI-21 regulates the expression of apoptosis-related proteins (Bax, Bcl-2) and Cyclin D1, and induces apoptosis.. ZSNI-21 can be used for the research of hepatocellular carcinoma, breast cancer, and non-small cell lung cancer.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C26H25N3O5
- Peso molecular:459.49
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
Actividad biológica
Descripciòn
IC50 & Target
[1]|
HDAC2 0.844 μM (IC50) |
HDAC6 0.106 μM (IC50) |
HDAC1 1.270 μM (IC50) |
Bax |
Bcl-2 |
In Vitro
ZSNI-21 (48 h) potently inhibits proliferation of Bel-7402, HCC-LM3, RBE, MCF-7, and A549 cancer cells with IC50 values ranging from 2.399 μM to 5.789 μM, while exhibiting low toxicity to HL-7702 and HEK 293 T normal cells[1].
ZSNI-21 functions as a dual inhibitor of ADAM17 and HDAC2 with IC50 values of 0.939 μM and 0.844 μM respectively, while also potently inhibiting HDAC6 (IC50 = 0.106 μM) and moderately inhibiting HDAC1 (IC50 = 1.270 μM)[1].
ZSNI-21 (6 h) exhibits strong intracellular binding affinity for ADAM17, HDAC1, HDAC2, and HDAC6 in Bel-7402 cells[1].
ZSNI-21 (1.5-12 μM; 48 h) reduces Notch intracellular domain (NICD) levels, increases acetylated histone H3 and H4 levels, modulates apoptosis-related proteins, and decreases Cyclin D1 expression in Bel-7402 cells[1].
ZSNI-21 (3-12 μM; 24 h) inhibits long-term proliferation and colony formation of Bel-7402 cells in a concentration-dependent manner[1].
ZSNI-21 (1.5-12 μM; 48 h) induces apoptosis in Bel-7402 cells in a concentration-dependent manner, as evidenced by apoptotic nuclear morphology and increased total apoptosis proportion (up to 40.2%)[1].
ZSNI-21 (1.5-6 μM; 48 h) inhibits migration of HCC-LM3 cells and reduces expression of EMT-related proteins in a concentration-dependent manner[1].
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:human hepatocellular carcinoma Bel-7402 cells
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Concentration:1.5 μM; 3 μM; 6 μM; 12 μM
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Incubation Time:48 h
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Result:Significantly reduced NICD levels in a concentration-dependent manner (with stronger inhibition than ADAM17 inhibitor JG26).
Significantly increased levels of acetylated histones H3 and H4 (comparable to HDAC inhibitor SAHA).
Downregulated pro-caspase-3 expression in a concentration-dependent manner.
Downregulated Cyclin D1 expression in a concentration-dependent manner.
Downregulated Bcl-2 expression in a concentration-dependent manner.
Upregulated Bax expression in a concentration-dependent manner.
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Cell Line:human hepatocellular carcinoma Bel-7402 cells
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Concentration:3 μM; 6 μM; 12 μM
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Incubation Time:24 h
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Result:Significantly reduced colony formation of Bel-7402 cells in a concentration-dependent manner, with colony formation rates decreasing notably at higher concentrations.
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Cell Line:human hepatocellular carcinoma Bel-7402 cells
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Concentration:1.5 μM; 3 μM; 6 μM; 12 μM
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Incubation Time:48 h
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Result:Induced nuclear shrinkage and chromatin condensation (apoptotic features) in treated cells via Hoechst 33342 staining.
Increased total apoptosis proportion from 7% in controls to 15.83% to 40.2% in treated cells in a concentration-dependent manner via Annexin V-FITC/PI flow cytometry.
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Cell Line:human highly invasive hepatocellular carcinoma HCC-LM3 cells
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Concentration:1.5 μM; 3 μM; 6 μM
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Incubation Time:48 h
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Result:Significantly inhibited HCC-LM3 cell migration in a concentration-dependent manner via wound healing scratch assay.
Significantly reduced vimentin expression in a concentration-dependent manner via immunofluorescence and Western blot.
Significantly reduced Slug expression in a concentration-dependent manner via Western blot.
Significantly reduced MMP9 expression in a concentration-dependent manner via Western blot.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female and male)[1]
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Dosage:2000 mg/kg
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Administration:i.g.; single dose; 14-day observation
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Result:Showed no mortality over the 14-day period.
Showed no significant weight loss over the 14-day period.
Showed no significant pathological changes in heart, liver, spleen, lung, and kidney compared to controls.
Chemical Information
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Peso molecular 459.49
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Fòrmula C26H25N3O5
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SMILES
COC(C=C1)=CC=C1OCCN2C(C)=C(C(NC3=CC=C(C(NO)=O)C=C3)=O)C4=C2C=CC=C4
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocolo
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Detection of 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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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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Liver Cancer Modeling
Liver cancer can be classified into primary liver cancer and secondary liver cancer. Secondary liver cancer is the metastatic liver cancer. Primary liver cancer includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, of which HCC is the most common form, accounting for approximately 90% of primary liver cancers[1]. HCC mouse models include chemical agent-induced models, transplanted tumor models, and genetic engineered models.
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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.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)