JN210
JN210 is a dual inhibitor of DCN1 and HDAC, with an IC50 of 94.26 nM against human DCN1. JN210 disrupts the UBE2M-DCN1 protein-protein interaction, blocks the neddylation modification of cullin-RING ligases, inhibits HDAC activity and induces histone hyperacetylation. JN210 impairs DNA damage repair function, induces cell apoptosis, exerts cytotoxicity and inhibits tumor growth. JN210 can be used for the research of non-small cell lung cancer.
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- Fòrmula: C24H30Cl2N4O3
- Peso molecular:493.43
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Descripciòn
IC50 & Target
[1]|
DCN1 94.26 nM (IC50) |
HDAC1 0.825 μM (IC50) |
HDAC2 2.369 μM (IC50) |
HDAC3 1.280 μM (IC50) |
HDAC6 0.253 μM (IC50) |
HDAC8 0.869 μM (IC50) |
HDAC11 2.894 μM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
1.4 μM
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Antiproliferative activity against human A549 nonsmall cell lung cancer cells assessed via cell proliferation inhibition assay.
Antiproliferative activity against human A549 nonsmall cell lung cancer cells assessed via cell proliferation inhibition assay.
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42593931 |
| NCI-H1299 | IC50 |
1.8 μM
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Antiproliferative activity against human H1299 nonsmall cell lung cancer cells assessed via cell proliferation inhibition assay.
Antiproliferative activity against human H1299 nonsmall cell lung cancer cells assessed via cell proliferation inhibition assay.
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42593931 |
| HepG2 | IC50 |
2.3 μM
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Antiproliferative activity against human HepG2 liver cancer cells assessed via cell proliferation inhibition assay.
Antiproliferative activity against human HepG2 liver cancer cells assessed via cell proliferation inhibition assay.
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42593931 |
In Vitro
JN210 potently inhibits the DCN1-UBE2M protein-protein interaction in a cell-free FP assay with an IC50 of 94.26 nM[1].
JN210 acts as a selective HDAC6 inhibitor in cell-free enzymatic assays, with an IC50 of 0.253 μM, and exhibits moderate activity against most Class I HDACs, negligible activity against Class IIa HDACs, and weak activity against HDAC11[1].
JN210 potently inhibits the proliferation of A549, H1299, and HepG2 cancer cells in vitro, with the highest potency in A549 cells (IC50 = 1.4 μM)[1].
JN210 (0.625-10 μM; 72 h) induces histone H3 and H4 hyperacetylation and upregulates Cullin1 and Cullin3 protein levels in A549 cells[1].
JN210 (1.25-10 μM; 24 h) induces concentration-dependent accumulation of acetylated α-tubulin in A549 cells, confirming HDAC6 target engagement[1].
JN210 (1.25-10 μM; 24 h) induces concentration-dependent upregulation of the p27 tumor suppressor in A549 cells, inhibiting Cullin3-mediated p27 degradation[1].
JN210 (1.25-10 μM; 24 h) induces concentration-dependent DNA double-strand breaks in A549 cells, as measured by elevated γ-H2A.X levels[1].
JN210 (3 μM; 24 h) alters global gene expression in A549 cells, with significant changes in genes related to cytoskeletal organization, cell cycle progression, protein degradation, and the PI3K/Akt signaling pathway[1].
JN210 (5-20 μM; 48 h) induces concentration-dependent G1 phase cell cycle arrest in A549 cells[1].
JN210 (5-10 μM; 48 h) induces concentration-dependent apoptosis in A549 cells, with greater efficacy at 10 μM than the equimolar physical combination of SAHA and NacM-OPT at a total concentration of 20 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A549 nonsmall cell lung cancer cells
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Concentration:0.625-10 μM
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Incubation Time:72 h
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Result:Induced concentration-dependent hyperacetylation of histone H3 and histone H4.
Markedly upregulated Cullin1 and Cullin3 protein levels.
Exerted minimal effect on DCN1 expression.
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Cell Line:A549 nonsmall cell lung cancer cells
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Concentration:1.25-10 μM
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Incubation Time:24 h
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Result:Induced concentration-dependent accumulation of acetylated α-tubulin.\nInduced concentration-dependent upregulation of p27 protein levels, with a more pronounced effect than the parent DCN1 inhibitor NacM-OPT alone.\nInduced concentration-dependent increases in γ-H2A.X protein levels, a marker of DNA double-strand breaks.
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Cell Line:A549 nonsmall cell lung cancer cells
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Concentration:5-20 μM
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Incubation Time:48 h
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Result:Induced concentration-dependent G1 phase arrest.
Caused a corresponding decrease in the S-phase cell population.
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Cell Line:A549 nonsmall cell lung cancer cells
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Concentration:5-10 μM
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Incubation Time:48 h
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Result:Induced concentration-dependent increases in apoptotic cells.
Induced apoptosis in over 60% of A549 cells at 10 μM.
Exerted a greater effect than the equimolar physical combination of SAHA and NacM-OPT (total 20 μM), which induced apoptosis in approximately 30% of cells.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 3.45 h | 0.12 h | 4857.2 ng/mL | 1064.7 ng·h/mL | 1285.6 ng·h/mL | 4.5 h | 4.9 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:i.p.; once daily; 15 days
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Result:Achieved a 44.6% tumor growth inhibition (TGI) rate at 10 mg/kg.
Achieved a 68.6% TGI rate at 30 mg/kg.
Caused no significant body weight loss at both doses.
Showed no obvious tissue damage via histopathological evaluation at both doses.
Chemical Information
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Peso molecular 493.43
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Fòrmula C24H30Cl2N4O3
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SMILES
O=C(NO)C1=CC=C(CN(C2CCN(CCCC)CC2)C(NC3=CC=C(Cl)C(Cl)=C3)=O)C=C1
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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.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
JN210 Related Classifications
HY-189074 Related Classifications
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