PROTAC BRD4 Degrader-48
PROTAC BRD4 Degrader-48 is a BRD4 degrader with a Kd of 0.69 μM for human BRD4 and a DC50 of 0.21 μM. PROTAC BRD4 Degrader-48 binds to BRD4 and GID4 to form a ternary complex, and induces ubiquitination and degradation of BRD4 via the ubiquitin-proteasome pathway. PROTAC BRD4 Degrader-48 inhibits proliferation and migration of tumor cells, blocks tumor growth, and maintains degrading activity even in VHL- and CRBN-deficient models. PROTAC BRD4 Degrader-48 can be used in studies related to renal cell carcinoma.
(Pink: BRD4 ligand (HY-78695); Blue: no E3 ligase ligand; Black: linker (HY-W014883)).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C49H64ClN9O3S
- 分子量:894.61
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保管条件:
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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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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生物活性
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BRD4 0.69 μM (Kd) |
BRD4 0.21 μM (DC50) |
PROTAC BRD4 Degrader-48 (compound a11) binds to purified GID4 protein with moderate affinity, with a KD value of 4.76 μM; it forms a stable cooperative ternary complex with BRD4-BD1 and GID4, with a ternary complex KD of 0.69 μM and a cooperativity factor of 6.90[1].
PROTAC BRD4 Degrader-48 (0.5-10 μM, 500 nM; 10 h) induces concentration-dependent degradation of BRD4-BD1 in HEK293T reporter cells[1].
PROTAC BRD4 Degrader-48 (14-3333 nM, 3 μM; 24 h, 2-24 h) induces efficient, concentration- and time-dependent degradation of BRD4 in VHL-deficient 786-O renal cell carcinoma cells, with a DC50 of 0.21 μM[1].
PROTAC BRD4 Degrader-48 (3 μM; 24 h, with 3 h pretreatment) mediates the degradation of BRD4 in VHL-deficient 786-O renal cell carcinoma cells via the ubiquitin-proteasome system[1].
PROTAC BRD4 Degrader-48 (3 μM; 24 h, 2 h pretreatment) induces BRD4 degradation in VHL-deficient 786-O renal cell carcinoma cells, a process that requires simultaneous binding to both BRD4 and GID4[1].
PROTAC BRD4 Degrader-48 (3 μM; 16 h) promotes the formation of the BRD4-a11-GID4 ternary complex in 786-O renal cell carcinoma cells and HEK293T cells expressing Flag-GID4[1].
PROTAC BRD4 Degrader-48 (3 μM; 24 h, 48 h siRNA transfection, 24 h transfection) induces strictly GID4-dependent BRD4 degradation in 786-O renal carcinoma cells and HEK293T cells[1].
PROTAC BRD4 Degrader-48 (1.5-3333 nM; 24 h) retains potent BRD4-degrading activity in CRBN-deficient 786-O renal cell carcinoma (RCC) cells, and can overcome resistance to PROTACs targeting CRBN and VHL[1].
PROTAC BRD4 Degrader-48 (0.12-10 μM; 24 h) induces concentration-dependent degradation of BRD4 in MDA-MB-231 breast cancer cells and A549 lung cancer cells, and its potency correlates with the intracellular expression level of GID4[1].
PROTAC BRD4 Degrader-48 exhibits potent antiproliferative activity in both parental and CRBN-deficient 786-O renal cell carcinoma cells, with IC50 values of 4.40 μM and 5.00 μM, respectively[1].
PROTAC BRD4 Degrader-48 (3 μM; 12 h, 24 h) potently inhibits the lateral migration of VHL-deficient 786-O renal cell carcinoma cells at a concentration of 3 μM[1].
PROTAC BRD4 Degrader-48 (1.5-3 μM; 24 h) inhibits Transwell migration of VHL-deficient 786-O renal cell carcinoma cells in a dose-dependent manner, and exhibits stronger efficacy than MZ1 (HY-107425) at concentrations of 1.5 μM and 3 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:VHL-deficient 786-O renal cell carcinoma (RCC) cells
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Concentration:14, 41, 123, 370, 1111, 3333 nM
3 μM -
Incubation Time:24 h
2, 4, 6, 8, 12, 24 h -
Result:Induced concentration-dependent BRD4 degradation with a DC50 of 0.21 μM after 24 h treatment.
Caused ~50% BRD4 degradation within 8 h and nearly complete degradation after 24 h at 3 μM.
Showed no hook effect at concentrations up to 30 μM.
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Cell Line:VHL-deficient 786-O renal cell carcinoma (RCC) cells
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Concentration:3 μM
100 nM MLN7243 (HY-100487), 1 μM MG132 (HY-13259) (pretreatment) -
Incubation Time:24 h
3 h (pretreatment) -
Result:Completely blocked BRD4 degradation when co-treated with MLN7243 or MG132.
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Cell Line:VHL-deficient 786-O renal cell carcinoma (RCC) cells
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Concentration:3 μM
3 μM JQ1 (HY-13030), 3 μM PFI-7 (HY-D2259), 3 μM compound 2 (pretreatment) -
Incubation Time:24 h
2 h (pretreatment) -
Result:Rescued BRD4 levels from degradation when pretreated with JQ1, PFI-7, or compound 2, with PFI-7 showing stronger blocking efficacy than compound 2.
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Cell Line:VHL-deficient 786-O renal cell carcinoma (RCC) cells, HEK293T cells
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Concentration:3 μM
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Incubation Time:24 h; 48 h (siRNA transfection, 786-O), 24 h (transfection, HEK293T)
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Result:Markedly attenuated BRD4 degradation when GID4 was silenced in 786-O cells.
Fully restored BRD4 degradation after GID4 knockdown when Flag-GID4 was ectopically re-expressed in HEK293T cells.
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Cell Line:786-O cells, CRBN-knockout (KO) 786-O renal cell carcinoma (RCC) cells
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Concentration:0.16, 0.31, 0.63, 1.3, 2.5, 5.0, 10 nM (786-O cells)
1.5, 4.5, 14, 41, 123, 370, 1111, 3333 nM (CRBN-KO 786-O cells) -
Incubation Time:24 h
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Result:Retained robust concentration-dependent BRD4 degradation activity, while MZ1 and dBET1 completely lost degradation activity.
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Cell Line:MDA-MB-231 breast cancer cells, A549 lung cancer cells
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Concentration:0.12, 0.37, 1.1, 3.3, 10 μM
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Incubation Time:24 h
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Result:Induced concentration-dependent BRD4 degradation in both cell lines, with a DC50 of 1.33 μM in A549 cells and 8.80 μM in MDA-MB-231 cells, efficacy correlating with basal GID4 expression levels.
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Cell Line:VHL-deficient 786-O renal cell carcinoma (RCC) cells
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Concentration:3 μM
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Incubation Time:12 h, 24 h
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Result:Significantly delayed scratch closure at 12 and 24 h, showing strong inhibition of lateral cell migration, while MZ1 had little effect.
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Cell Line:VHL-deficient 786-O renal cell carcinoma (RCC) cells
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Concentration:1.5, 3 μM
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Incubation Time:24 h
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Result:Markedly reduced the number of migrating cells in a dose-dependent fashion, with a more potent inhibitory effect than MZ1.
| Species | Dose | Route | T1/2 | Cmax | AUCinf | F |
|---|---|---|---|---|---|---|
| Mice[1] | 15 mg/kg | i.p. | 3.52 h | 4273.43 ng/mL | 15422.47 ng·h/mL | 3.48 % |
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 (female, 5 weeks old)[1]
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Dosage:15 mg/kg; 30 mg/kg
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Administration:i.p.; every other day; 14 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 54% at 15 mg/kg.
Achieved a tumor growth inhibition (TGI) rate of 67% at 30 mg/kg.
Induced extensive necrosis, marked disruption of tumor structural integrity, pronounced reduction in Ki67-positive proliferating cells, and significant BRD4 degradation in tumor tissues.
Caused no significant effect on mouse body weight.
Showed normal tissue architecture without pathological alterations in major organs (heart, liver, spleen, lung, kidney) via histopathological analysis.
化学情報
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分子量 894.61
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分子式 C49H64ClN9O3S
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SMILES
O=C(C[C@H]1C2=NN=C(N2C3=C(C(C4=CC=C(C=C4)Cl)=N1)C(C)=C(S3)C)C)NCCCCCCCCCCCCNC([C@@H]5CC[C@@H](CC5)NC(CNCC6=CC7=C(C=CC=C7)N6)=O)=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
PROTAC BRD4 Degrader-48 関連分類
HY-184923 関連分類
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