DNMT-IN-6
DNMT-IN-6 is a DNA methyltransferase inhibitor with activity against DNMT1, DNMT3A, and DNMT3B. DNMT-IN-6 drives demethylation, and restores TMS1 tumor suppressor gene expression. DNMT-IN-6 induces apoptosis, causes G2/M phase arrest, disrupts mitochondrial integrity, and activates the intrinsic caspase cascade (3/7/9). DNMT-IN-6 inhibits tumor growth, and improves survival in xenograft models. DNMT-IN-6 can be used for the research of cancer, such as diffuse large B-cell lymphoma.
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- CAS No.: 3038316-36-5
- Formule: C19H18AsNO3S2
- Masse moléculaire:447.40
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Activité biologique
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Chemical Information
- Pureté et documentation
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Activité biologique
Description
IC50 & Target
[1]|
Caspase 3 |
Caspase 9 |
DNMT1 |
DNMT3A |
DNMT3B |
In Vitro
DNMT-IN-6 (Compound CZ2) (0.2-1.4 μM; 24-48 h) potently inhibits proliferation of SUDHL-4, SUDHL-6, and DB DLBCL cell lines in a dose- and time-dependent manner, with 24 h IC50 values of 0.67 μM, 0.72 μM, and ~0.90 μM respectively, and exhibits minimal cytotoxicity to normal HK-2 and MIN-6 cells[1].
DNMT-IN-6 (1 μM; 24 h) induces mitochondrial membrane depolarization in SUDHL-4 and SUDHL-6 DLBCL cells[1].
DNMT-IN-6 (1 μM; 24 h) significantly induces apoptosis in SUDHL-4 and SUDHL-6 DLBCL cells, and activates caspase-3 and caspase-9[1].
DNMT-IN-6 (1 μM; 24 h) reduces intracellular ATP levels in SUDHL-4 and SUDHL-6 DLBCL cells[1].
DNMT-IN-6 (1 μM; 24 h) induces G2/M cell cycle arrest in SUDHL-6 DLBCL cells[1].
DNMT-IN-6 (1 μM; 24 h) reduces TMS1 promoter methylation, increases TMS1 expression, and decreases DNMT1, DNMT3A, and DNMT3B expression in SUDHL-4 and SUDHL-6 DLBCL cells[1].
DNMT-IN-6 (1 μM; 24 h) inhibits the binding of DNMT3A to the TMS1 promoter in SUDHL-4 DLBCL cells, contributing to TMS1 promoter demethylation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:diffuse large B-cell lymphoma (DLBCL) cell lines SUDHL-4, SUDHL-6, DB; normal human cell lines HK-2, MIN-6
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Concentration:0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4 μM
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Incubation Time:24, 36. 48 h
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Result:Inhibited proliferation of DLBCL cells in a dose- and time-dependent manner.
Reduced IC50 in SUDHL-4 cells to 0.67±0.08 μM at 24 h, and 0.38±0.05 μM at 48 h.
Reduced IC50 in SUDHL-6 cells to 0.72±0.09 μM at 24 h, and 0.41±0.06 μM at 48 h.
Maintained an IC50 of ~0.90 μM in DB cells across 24-48 h.
Showed minimal cytotoxicity to HK-2 and MIN-6 normal cells at 1 μM for 24 h.
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Cell Line:DLBCL cell lines SUDHL-4, SUDHL-6
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Concentration:1 μM
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Incubation Time:24 h (CZ2 treatment); 1 h (Z-VAD-FMK pre-incubation)
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Result:Significantly increased the percentage of apoptotic (Annexin V+/PI- early apoptotic and Annexin V+/PI+ late apoptotic/necrotic) cells in SUDHL-4 and SUDHL-6 cells.
Was effectively blocked by pre-incubation with Z-VAD-FMK (HY-16658B) in SUDHL-4 cells.
Increased caspase-3 and caspase-9 levels.
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Cell Line:DLBCL cell line SUDHL-6
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Concentration:1 μM
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Incubation Time:24 h
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Result:Induced G2/M cell cycle arrest in SUDHL-6 cells, with a significant increase in the percentage of cells in G2/M phase.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ | C0 | Vss | Vz | CL |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 3.5 mg/kg | i.v. | 2.68 h | 0.083 h | 1155.00 ng/mL | 572.26 | 617.02 | 1.37 h | 2.18 h | 3121.62 ng/mL | 13.60 L/kg | 23.68 L/kg | 99.50 mL/min/kg |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (4-6 week-old male; subcutaneous xenograft via injection of 1×107 SUDHL-4 cells)[1]
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Dosage:3.5 mg/kg
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Administration:i.p.; every other day; 12 days
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Result:Achieved 71.39% tumor growth inhibition.
Significantly reduced final tumor weight compared to controls.
Significantly prolonged overall survival of tumor-bearing mice.
Significantly upregulated TMS1 protein expression and downregulated DNMT3A protein expression in tumor tissue.
Showed no significant alteration in peripheral white blood cell counts, no significant histopathological changes in heart, liver, or kidney tissues, and no significant difference in kidney injury markers KIM-1 and NGAL relative to controls.
Chemical Information
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CAS No. 3038316-36-5
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Masse moléculaire 447.40
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Formule C19H18AsNO3S2
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SMILES
O=C(NC1=CC=C(C=C1)[As]2SCCCS2)/C=C/C3=CC4=C(OCO4)C=C3
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DNMT-IN-6 Related Classifications
HY-182009 Related Classifications
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