DBr-1
Based on 1 Customer Validation
DBr-1 is a potent BRD9 PROTAC degrader with a DC50 of 90 nM. DBr-1 mediates the ubiquitination and proteasomal degradation of BRD9 via the ubiquitin-proteasome pathway. DBr-1 is applicable to research related to renal cell carcinoma and synovial sarcoma.
(Pink: BRD9 ligand (HY-100352); Blue: Cereblon ligand (HY-149934); Black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.87%
- Fòrmula: C55H68ClN9O5
- Peso molecular:970.64
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Almacenamiento:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
BRD9 90 nM (DC50) |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | DC50 |
500 nM
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BRD9 degradation in HEK293 BRD9-HiBiT/FF/CAS9 cells assessed via immunoblotting after 6-hour incubation.
BRD9 degradation in HEK293 BRD9-HiBiT/FF/CAS9 cells assessed via immunoblotting after 6-hour incubation.
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38177131 |
| HEK293 | DC50 |
90 nM
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BRD9 degradation in HEK293 BRD9-HiBiT/FF/CAS9 cells assessed via HiBiT luminescence assay after 6-hour incubation.
BRD9 degradation in HEK293 BRD9-HiBiT/FF/CAS9 cells assessed via HiBiT luminescence assay after 6-hour incubation.
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38177131 |
| HEK293 | DC50 |
193 nM
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BRD9 protein degradation activity in HEK293 BRD9-HiBIT CAS9/FF cells assessed via luminescence-based assay after 2 h incubation.
BRD9 protein degradation activity in HEK293 BRD9-HiBIT CAS9/FF cells assessed via luminescence-based assay after 2 h incubation.
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2023.04.09.536153v2.abstract |
In Vitro
DBr-1 binds to purified DCAF1 with sub-micromolar potency, and forms a stable, cooperative ternary complex with DCAF1 and BRD9, as measured by TR-FRET and SPR assays[1].
DBr-1 (62.5-1000 nM; 0.5-48 h) potently and rapidly degrades BRD9 in HEK293 BRD9-HiBiT/FF/CAS9 cells via the ubiquitin-proteasome pathway, with a DC50 of 90 nM[1].
DBr-1 (0.001-10 μM; 2 h) effectively degrades BRD9 in VHL-deficient 768-O cells with a DC50 of 1.039 μM, providing an alternative to VHL-based PROTACs in cells with intrinsic VHL loss[1].
DBr-1 (2 h) induces BRD9 degradation in HEK293 BRD9-HiBIT CAS9/FF cells with a DC50 of 193 nM after 2 h incubation, dependent on the ubiquitin-proteasome pathway[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293 BRD9-HiBiT/FF/CAS9 cells
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Concentration:62.5-1000 nM (dose-response); 1000 nM (time-course); 1000 nM NAE1i, 1000 nM proteasome inhibitor, 1000 nM UAE1i (pre-incubation), 1000 nM DBr-1 (post-pre-incubation)
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Incubation Time:6 h (dose-response); 0.5-48 h (time-course); 2 h (pre-incubation), 2 h (post-pre-incubation)
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Result:Induced ~90% BRD9 loss at 1000 nM after 6 hours, with an estimated DC50 of ~500 nM from immunoblotting, and a DC50 of 90 nM from HiBiT assays.
Caused rapid BRD9 degradation, reaching ~90% after 30 minutes, maintained for over 6 hours, and showed slow rebound at 24 and 48 hours.
Had its mediated BRD9 degradation fully rescued by pre-treatment with NAE1i, proteasome inhibitor, or UAE1i.
Did not reduce BRD9 levels when compared to individual DCAF1 binder (13) or BRD9 binder (BI-9564) at 1000 nM.
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Cell Line:768-O cells (VHL-deficient)
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Concentration:0.001-10 μM
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Incubation Time:2 h
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Result:Degraded BRD9 in 768-O cells with a DC50 of 1.039 μM.
Showed activity while the VHL-based BRD9 PROTAC VZ185 showed no activity in this VHL-deficient cell line.
Chemical Information
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Appearance Solid
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Peso molecular 970.64
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Fòrmula C55H68ClN9O5
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Color Off-white to light yellow
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SMILES
COC1=C(C(C2=C3C=NC=C2)=CN(C)C3=O)C=C(OC)C(CN4CCC(OCCCCCC(N5CCN(C6=CC=C7C(N=C(C8(C9=CC=C(Cl)C=C9)CCCCC8)N=C7NCCN)=C6)CC5)=O)CC4)=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (103.02 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (280 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.0302 mL | 5.1512 mL | 10.3025 mL | 25.7562 mL |
| 5 mM | 0.2060 mL | 1.0302 mL | 2.0605 mL | 5.1512 mL | |
| 10 mM | 0.1030 mL | 0.5151 mL | 1.0302 mL | 2.5756 mL | |
| 15 mM | 0.0687 mL | 0.3434 mL | 0.6868 mL | 1.7171 mL | |
| 20 mM | 0.0515 mL | 0.2576 mL | 0.5151 mL | 1.2878 mL | |
| 25 mM | 0.0412 mL | 0.2060 mL | 0.4121 mL | 1.0302 mL | |
| 30 mM | 0.0343 mL | 0.1717 mL | 0.3434 mL | 0.8585 mL | |
| 40 mM | 0.0258 mL | 0.1288 mL | 0.2576 mL | 0.6439 mL | |
| 50 mM | 0.0206 mL | 0.1030 mL | 0.2060 mL | 0.5151 mL | |
| 60 mM | 0.0172 mL | 0.0859 mL | 0.1717 mL | 0.4293 mL | |
| 80 mM | 0.0129 mL | 0.0644 mL | 0.1288 mL | 0.3220 mL | |
| 100 mM | 0.0103 mL | 0.0515 mL | 0.1030 mL | 0.2576 mL |
DBr-1 Related Classifications
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