HL435
HL435 is a BRD4 PROTAC degrader with DC50 values of 11.9 nM (MDA-MB-231 cells) and 21.9 nM (MCF-7 cells), respectively. HL435 recruits the CRL4DCAF11 E3 ubiquitin ligase complex to degrade BRD4 via the ubiquitin-proteasome system. HL435 induces cell cycle arrest and apoptosis (apoptosis) in cancer cells, downregulates the expression levels of cyclin D1 and cyclin B1, activates caspase-9, and induces PARP1 cleavage. HL435 exerts anti-tumor activity both in vitro and in mouse xenograft tumor models. HL435 can be used for the research of breast cancer and prostate cancer.
(Pink: BRD4 ligand (HY-78695); Blue: DCAF11 ligand (HY-161770); Black: linker (HY-W004640)).
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- Fòrmula: C47H48BrClF3N7O7S
- Peso molecular:1027.34
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
BRD4 |
Caspase 9 |
PARP-1 |
In Vitro
HL435 (H27) (0-1000 nM; 1-24 h) potently degrades BRD4 in MDA-MB-231 and MCF-7 cells, with DC50 values of 11.9 nM and 21.9 nM, respectively, and a maximum degradation efficiency of >99%[1].
HL435 (0-1.0 μM; 6 h) induces BRD4 degradation in MDA-MB-231 cells as well as WT-, ATG5KO-, and ATG4BKO-HeLa cells, and this process is independent of the autophagy-lysosome pathway[1].
HL435 (0-2.0 μM; 6-8 h) induces BRD4 degradation in MDA-MB-231 and HEK293T cells via the ubiquitin-proteasome system, a process that requires activation of functional Cullin-RING E3 ligases[1].
HL435 (50-5000 nM; 6-24 h) recruits the CRL4DCAF11 E3 ubiquitin ligase complex, mediates proteasomal degradation of BRD4 in CRISPRi HEK293T cells, and forms a ternary complex with BRD4 and DCAF11[1].
HL435 (48 h) potently inhibits the proliferation of 22RV1, MDA-MB-31, MCF7, and A549 cells, with IC50 values of 8.7, 205, 378, and 1380 nM, respectively[1].
HL435 (0.25-1.5 μM; 24 h) induces concentration-dependent cell cycle arrest in MCF-7 cells, blocking G0/G1 phase transition at low concentrations and G2/M phase transition at high concentrations[1].
HL435 (0.5-1.0 μM; 24-36 h) potently induces apoptosis in MDA-MB-231 cells, with the apoptosis rate reaching 55.9% upon treatment with 1.0 μM for 36 h, and activates caspase-9 as well as induces PARP1 cleavage[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 cells, MCF-7 cells
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Concentration:0, 0.1, 1, 10, 100, 500, 1000 nM (12 h treatment); 0.5 μM (time-course treatment)
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Incubation Time:12 h (concentration gradient); 1, 3, 6, 12, 24 h (0.5 μM treatment)
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Result:Achieved a maximum BRD4 degradation efficiency (Dmax) >99% in both cell lines.
Exhibited DC50 values of 11.9 nM in MDA-MB-231 cells and 21.9 nM in MCF-7 cells.
Induced detectable BRD4 degradation 1 hour after treatment, with protein half-lives of 1.38 hours in MDA-MB-231 cells and 1.31 hours in MCF-7 cells.
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Cell Line:human breast cancer MCF-7 cells, human breast cancer MDA-MB-231 cells
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Concentration:0.25, 0.5, 1.5 μM HL435 (MCF-7 flow cytometry); 1.0 μM HL435 (protein analysis)
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Incubation Time:24 h
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Result:Arrested MCF-7 cells at the G0/G1 phase at 0.25 μM, and at the G2/M phase at 1.5 μM.
Upregulated P53 and P21 levels and downregulated cyclin D1 and cyclin B1 levels in MCF-7 cells via western blot.
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Cell Line:human breast cancer MDA-MB-231 cells
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Concentration:0.5, 1 μM HL435 (flow cytometry); 1 μM HL435 (protein analysis)
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Incubation Time:36 h (flow cytometry); 24 h (protein analysis)
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Result:Resulted in an apoptotic rate of 55.9% in MDA-MB-231 cells at 1.0 μM for 36 hours, which was over 20-fold more potent than JQ1.
Increased levels of cleaved caspase-9 and PARP1 via western blot.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID (female, 6 to 7 weeks old, subcutaneous xenograft of MDA-MB-231 cells)[1]
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Dosage:20 mg/kg
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Administration:i.p.; daily, 6 days per week; 27 days
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Result:Achieved a tumor growth inhibition rate (TGI) of 54.34%.
Reduced tumor weight by 51.12% compared to the vehicle group.
Showed body weight comparable to vehicle-treated mice, with no obvious toxicity observed.
Chemical Information
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Peso molecular 1027.34
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Fòrmula C47H48BrClF3N7O7S
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SMILES
O=C(COC1=C(/C=C(C(C=CC(C(F)(F)F)=C2)=C2N3)\C3=O)C=C(Br)C=C1)NCCCOCCOCCOCCCNC(C[C@H]4C5=NN=C(C)N5C(SC(C)=C6C)=C6C(C7=CC=C(Cl)C=C7)=N4)=O
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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)
HL435 Related Classifications
HY-161769 Related Classifications
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Keywords
- HL435
- HL 435
- HL-435
- PROTACs
- Epigenetic Reader Domain
- Apoptosis
- Caspase
- PARP
- breast cancer
- ubiquitin-proteasome system
- MDA-MB-231 human breast cancer cells
- BRD4
- CRL4DCAF11 E3 ubiquitin ligase complex
- MCF-7 human breast cancer cells
- 22RV1 prostate cancer cells
- HEK293T cells
- mouse xenograft tumor models
- prostate cancer
- Inhibitor
- inhibitor
- inhibit