PROTAC BET Degrader-16
PROTAC BET Degrader-16 (Compound A10) is a BET PROTAC degrader with a DC50 of 0.31 nM against BRD4, and it preferentially targets BRD4 over other BET family members. PROTAC BET Degrader-16 degrades BRD2, BRD3 and BRD4 via the ubiquitin-proteasome system, a process that requires target binding and recruitment of the CRBN E3 ligase. PROTAC BET Degrader-16 induces cell cycle arrest and promotes apoptosis. PROTAC BET Degrader-16 exerts anti-tumor activity against acute myeloid leukemia.
(Pink: BET Target protein ligand; Blue: Cereblon ligand (HY-A0003); Black: linker (HY-W018678)).
For research use only. We do not sell to patients.
- CAS No.: 2410947-65-6
- Formula: C44H45F2N7O9S
- Molecular Weight:885.93
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
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BRD4 0.31 nM (DC50) |
BRD2 6.44 nM (DC50) |
BRD3 7.93 nM (DC50) |
Cereblon |
PROTAC BET Degrader-16 binds directly to BRD4 (BD1) with an IC50 of 3.0 nM[1].
PROTAC BET Degrader-16 (72 h) potently inhibits the proliferation of MV4-11 leukemia cells with an IC50 value of 1.964 nM, while it exhibits low activity in RAMOS cells[1].
PROTAC BET Degrader-16 (0.1-300 nM; 1-24 h) efficiently and selectively degrades BRD2, BRD3 and BRD4 in a time- and concentration-dependent manner in MV4-11 cells, with a DC50 of 0.31 nM for BRD4. Its mechanism of action depends on BRD4 binding, CRBN recruitment, and the ubiquitin-proteasome system[1].
PROTAC BET Degrader-16 (1-100 nM) induces dose-dependent S-phase arrest in MV4-11 cells[1].
Treatment of MV4-11 cells with PROTAC BET Degrader-16 (0.3-100 nM; 48 h) for 48 h induces concentration-dependent apoptosis, and its activity is significantly higher than that of ABBV-075 (HY-100015)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 cells
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Concentration:0.1-300 nM (concentration-dependent degradation); 100 nM (time-dependent degradation, complete degradation, mechanism studies)
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Incubation Time:24 h (concentration-dependent degradation, complete degradation, mechanism studies); 1, 2, 4, 8, 14, 24 h (time-dependent degradation)
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Result:Induced nearly complete loss of BRD2, BRD3, and BRD4 protein at 100 nM for 24 h, with concurrent downregulation of c-Myc.
Exhibited a DC50 of 6.44 ± 0.18 nM for BRD2, 7.93 ± 0.73 nM for BRD3, and 0.31 ± 0.08 nM for BRD4.
Showed time-dependent degradation, with effects observed as early as 1 h post-treatment at 100 nM.
Abolished degradation completely when cells were pre-treated with ABBV-075, lenalidomide, MLN4924, MG132, or carfilzomib.
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 to 5 weeks old; subcutaneous AML xenograft model)[1]
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Dosage:2 mg/kg; 6 mg/kg
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Administration:i.p.; every other day; 21 days
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Result:Achieved 48.8% tumor growth inhibition (TGI) and significantly downregulated BRD4 and c-Myc protein expression in tumor tissue compared to vehicle control at 2 mg/kg.
Achieved 76.2% TGI, with a more pronounced reduction in c-Myc protein expression than the 2 mg/kg dose at 6 mg/kg.
Caused no significant body weight loss in treated mice.
Resulted in no significant changes in hepatic (ALT, AST), renal, or cardiac (CK-MB, LDH) toxicity biomarkers compared to vehicle control at both doses.
Chemical Information
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CAS No. 2410947-65-6
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Molecular Weight 885.93
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Formula C44H45F2N7O9S
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SMILES
O=C(C(N1)=CC(C(C2=CC(NS(=O)(CC)=O)=CC=C2OC3=CC=C(F)C=C3F)=CN4C)=C1C4=O)NCCCCCCCC(NC5=CC=CC6=C5CN(C(CC7)C(NC7=O)=O)C6=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC BET Degrader-16 Related Classifications
HY-181867 Related Classifications
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