NEP162
NEP162 is a BRD4 PROTAC degrader based on the E3 ubiquitin ligase GID4, with DC50 values of 1.2 μM and 1.6 μM in SW480 and U2OS cells, respectively, and a Kd value of 0.13 µM for GID4. NEP162 bridges the E3 ligase GID4 and BRD4 to form a ternary complex, promotes polyubiquitination and subsequent degradation of BRD4 via the ubiquitin-proteasome system, reduces the proliferation capacity of tumor cells and induces apoptosis. NEP162 can be used for research on cancers such as osteosarcoma, colorectal cancer and non-small cell lung cancer.
(Pink: BRD4 ligand (HY-78695); Blue: GID4 ligand (HY-D2259); Black: linker).
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- CAS No.: 3031840-36-2
- Formule: C50H56ClN11O3S
- Masse moléculaire:926.57
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Stockage:
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
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Activité biologique
Description
IC50 & Target
[1]|
BRD4 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| SW480 | DC50 |
1.2 μM
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Half-maximal degradation of endogenous BRD4 in human SW480 colon cancer cells after 18 h treatment, measured via immunoblotting assay.
Half-maximal degradation of endogenous BRD4 in human SW480 colon cancer cells after 18 h treatment, measured via immunoblotting assay.
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40295770 |
| U2OS | DC50 |
1.6 μM
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Half-maximal degradation of endogenous BRD4 in human U2OS osteosarcoma cells after 18 h treatment, measured via immunoblotting assay.
Half-maximal degradation of endogenous BRD4 in human U2OS osteosarcoma cells after 18 h treatment, measured via immunoblotting assay.
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40295770 |
In Vitro
NEP162 (2 μM; 18 h) loses its ability to degrade BRD4 protein in GID4-knockdown SW480 cells[1].
NEP162 (0.2-10 μM; 18 h) promotes the polyubiquitination of BRD4 in U2OS cells that are pre-transfected to express Flag-BRD4 and HA-Ub and pre-treated with MG132 (HY-13259), and it exerts a BRD2-degrading effect without degrading BRD3 protein[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:U2OS and SW480 cells
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Concentration:0.1, 0.2, 0.5, 1, 2, 5, 10, 20 μM
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Incubation Time:6, 12, 18, 24 h
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Result:Decreased endogenous BRD4 protein levels in a dose-dependent manner.
Significantly reduced BRD4 protein levels over time, especially at 18 and 24 hours.
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Cell Line:U2OS cells
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Concentration:0.2, 0.5, 1, 2, 5, 10 μM
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Incubation Time:18 h
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Result:Reduced BRD2 protein levels, but did not alter BRD3 protein expression levels.
Significantly increased the polyubiquitination levels of BRD4.
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Cell Line:U2OS cells
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Concentration:0.5, 2, 5 μM
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Incubation Time:24, 48, 72 h
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Result:Significantly inhibited cell viability and proliferation in a dose- and time-dependent manner.
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Cell Line:U2OS cells
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Concentration:2 μM
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Incubation Time:24 h
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Result:Significantly reduced the percentage of EdU-positive cells, effectively inhibiting cell proliferation.
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Cell Line:U2OS cells
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Concentration:2 μM
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Incubation Time:24 h
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Result:Significantly increased the percentage of TUNEL-positive cells, inducing tumor cell apoptosis.
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Cell Line:U2OS cells
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Concentration:2 μM
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Incubation Time:7 days
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Result:Significantly inhibited the colony-forming ability of cells and reduced the number of colonies.
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Cell Line:U2OS cells
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Concentration:2 μM
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Incubation Time:18 h
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Result:Had no significant effect on the mRNA transcription levels of BRD2, BRD3, and BRD4.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUClast | AUCinf |
|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 1.76 h | 0.83 h | 2.68 μM | 6.68 μM·h | 6.96 μM·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:BALB/c nude mice were injected subcutaneously with 5×106 U2OS cells[1]
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Dosage:5 mg/kg; 10 mg/kg; 15 mg/kg
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Administration:i.p.; every other day; 14 days
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Result:Showed modest tumor growth inhibition at 5 mg/kg.
Notably suppressed tumor growth at 10 mg/kg and 15 mg/kg, with near-complete inhibition at 15 mg/kg.
Increased TUNEL-positive apoptotic cells and reduced Ki67-positive proliferative cells in a dose-dependent manner.
Markedly reduced BRD4 levels in tumor tissues at 10 mg/kg and 15 mg/kg.
Did not affect mouse body weight.
Showed no apparent physiological damage to vital organs via H&E staining.
Chemical Information
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CAS No. 3031840-36-2
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Masse moléculaire 926.57
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Formule C50H56ClN11O3S
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SMILES
O=C(N[C@@H]1CC[C@H](C2=NC(C=CC(OCCCN3CCN(C(C[C@H]4C5=NN=C(C)N5C(SC(C)=C6C)=C6C(C7=CC=C(Cl)C=C7)=N4)=O)CC3)=C8)=C8N2)CC1)CNCC(N9)=CC%10=C9C=CC=C%10
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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)
NEP162 Related Classifications
HY-174996 Related Classifications
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