BETd-246
Based on 2 publication(s) in Google Scholar
BETd-246 is a BRD2/3/4 PROTAC degrader targeting the BET family. BETd-246 induces ubiquitination and proteasomal degradation of BRD2, BRD3 and BRD4 by recruiting the CUL4-RBX1-DDB1-CRBN E3 ubiquitin ligase complex; it also inhibits TRAT1 expression and depletes BET proteins. BETd-246 suppresses cancer cell proliferation and invasion, disrupts the cell cycle and induces apoptosis. BETd-246 is applicable to research related to triple-negative breast cancer and T-cell acute lymphoblastic leukemia.
(Pink: BET ligand (HY-122703); Blue: Cereblon ligand (HY-103596); Black: linker (HY-128844)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza : 98.34%
- No. CAS: 2140289-17-2
- Fòrmula: C48H55N11O10
- Peso molecular:946.02
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Almacenamiento:
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
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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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Publications Citing Use of MedChemExpress (MCE) BETd-246
MoreVer todos los productos específicos de isoformas PROTACs
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
BRD2 |
BRD3 |
BRD4 |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Burkitts lymphoma cell | GI50 |
0.4 μM
Compound: BETd-246; 6
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Antiproliferative activity against human Burkitts lymphoma cells
Antiproliferative activity against human Burkitts lymphoma cells
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[PMID: 36202064] |
| MDA-MB-468 | IC50 |
<10 nM
Compound: BETd-246; 6
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Antiproliferative activity against human MDA-MB-468 cells
Antiproliferative activity against human MDA-MB-468 cells
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[PMID: 36202064] |
| MV4-11 | IC50 |
1.24 μM
Compound: BETd-246; 6
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Cytotoxicity against human MV4-11 cells
Cytotoxicity against human MV4-11 cells
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[PMID: 36202064] |
| MV4-11 | IC50 |
6 nM
Compound: BETd-246; 6
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Cytotoxicity against human MV4-11 cells measured after 96 hrs
Cytotoxicity against human MV4-11 cells measured after 96 hrs
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[PMID: 36202064] |
| NAMALVA | GI50 |
0.34 μM
Compound: BETd-246; 6
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Antiproliferative activity against human NAMALVA cells
Antiproliferative activity against human NAMALVA cells
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[PMID: 36202064] |
In Vitro
BETd-246 (10-100 nM; 1-3 h) potently and selectively depletes BRD2, BRD3 and BRD4 in the MDA-MB-468 cell line via a proteasome-dependent mechanism mediated by the CRL4CRBN E3 ligase, with nearly complete depletion achieved within 1-3 h[1].
BETd-246 (3-8 h) induces a unique transcriptional response in human MDA-MB-157, MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) cell lines, and downregulates gene expression primarily in a BET degradation-dependent manner, including key proliferation and survival genes such as BRD2 and MCL1[1].
BETd-246 (24 h) inhibits cell viability in a concentration-dependent manner, with nanomolar IC50 values: MOLT4 (304.02 nM), 6T-CEM (407.2 nM), Jurkat (118.5 nM), J.gamma1 (580.2 nM), SUPT1 (320.2 nM), CCRF-CEM (307.72 nM), PF382 (441.72 nM), and CD3+ T cells (1430 nM)[2].
BETd-246 (500-2000 nM; 24 h) induces irregular cell morphology and formation of cellular debris in J.gamma1 and 6T-CEM T-ALL cells[2].
BETd-246 (500 nM) significantly reduces the colony-forming ability of J.gamma1 and 6T-CEM T-ALL cells[2].
BETd-246 (5-10 nM) significantly downregulates the expression of TRAT1 mRNA in J.gamma1 T-ALL cells[2].
BETd-246 (100 nM; 5-48 h) induces robust, CRBN-dependent apoptosis in the MDA-MB-468 cell line by activating multiple apoptotic pathways, and cleavage of key apoptotic markers is detectable within 5 h of treatment[1].
BETd-246 (10 nM) downregulates the expression of MCL1 in human triple-negative breast cancer (TNBC) cell lines, and this downregulation plays a critical role in the potent apoptosis induction and growth inhibition mediated by BETd-246[1].
Treatment with BETd-246 (500-2000 nM; 24 h) induces concentration-dependent apoptosis in J.gamma1 and 6T-CEM T-ALL cells, with significantly higher apoptosis rates at higher concentrations[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-468
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Concentration:10 nM, 30 nM, 100 nM
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Incubation Time:1 h, 2 h, 3 h
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Result:Caused dose-dependent depletion of BRD2, BRD3, and BRD4 in TNBC cell lines.
Achieved near-complete depletion of these proteins with 30-100 nM for 1 h or 10-30 nM for 3 h.
Had its induced BET protein depletion blocked by pre-treatment with excess thalidomide, BETi-211, PR-171, or MLN4924.
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Cell Line:MDA-MB-468 cells
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Concentration:100 nM
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Incubation Time:5 h, 24 h (cell cycle analysis), 48 h (apoptosis analysis)
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Result:Induced robust apoptosis in most TNBC cell lines.
Caused profound cleavage of caspase-3 and PARP, and activation of caspase-3/7 at 10 nM.
Activated caspase-2, -8, and -9 in MDA-MB-468 cells, with cleavage of caspase-8, -9, and -3 observed within 5 h of treatment.
Had its induced PARP cleavage blocked by CRBN silencing.
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Cell Line:J.gamma1, 6T-CEM, Jurkat
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Concentration:500 nM, 1000 nM, 2000 nM
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Incubation Time:48 h
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Result:Degraded BRD2, BRD3, and BRD4 proteins in a concentration-dependent manner, with a particularly pronounced effect on BRD4; BRD4 protein levels were almost completely diminished in treated cells.
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Cell Line:J.gamma1, 6T-CEM
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Concentration:500 nM, 1000 nM, 2000 nM
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Incubation Time:24 h
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Result:Induced concentration-dependent increases in early and late apoptosis: in J.gamma1 cells, apoptotic rates rose from ~3% (control) to ~18% (500 nM) and ~27% (2000 nM); in 6T-CEM cells, apoptotic rates rose from ~4% (control) to ~16% (500 nM) and ~22% (1000 nM), with statistically significant differences.
In Vivo
BETd-246 (5 mg/kg; i.v.; 3 times per week; 2 weeks) inhibits MDA-MB-453 breast cancer xenograft growth in SCID mice with 85% TGI, with no significant toxicity[1].
BETd-246 (10 mg/kg; i.v.; 3 times per week; 2-3 weeks) exhibits very limited antitumor activity against MDA-MB-231 breast cancer xenografts in SCID mice, with no significant toxicity[1].
BETd-246 (10 mg/kg; i.v.; 3 times per week; 2-3 weeks) shows no antitumor activity against MDA-MB-468 breast cancer xenografts in SCID mice, with no significant toxicity[1].
BETd-246 (0.5 mg/kg; i.p.; daily; 9 days) significantly reduces T-ALL cell proliferation, invasion, and BRD4 expression in NSG mice, and prolongs mouse survival with good tolerability[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID mice[1]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.v.; 3 times per week; 3 weeks
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Result:Inhibited WHIM24 tumor growth, with activity comparable to BETi-211 at 50 mg/kg daily oral dosing.
Induced partial tumor regression during treatment at 10 mg/kg.
Reduced BET protein levels by > 80% in tumors as early as 1 hour after a single 10 mg/kg dose, with effect lasting at least 9 hours.
Markedly reduced MCL1 protein levels in tumors by 3 hours post 10 mg/kg treatment.
Caused no significant weight loss or apparent toxicity.
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Animal Model:SCID mice[1]
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Dosage:5 mg/kg
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Administration:i.v.; 3 times per week; 2 weeks
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Result:Significantly inhibited MDA-MB-453 tumor growth, achieving a tumor growth inhibition (TGI) percentage of 85% at the end of the study.
Caused no significant weight loss or apparent toxicity.
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Animal Model:SCID mice[1]
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Dosage:10 mg/kg
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Administration:i.v.; 3 times per week; 2-3 weeks
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Result:Exhibited very limited antitumor activity in the MDA-MB-231 xenograft model.
Caused no significant weight loss or apparent toxicity.\nShowed no antitumor activity in the MDA-MB-468 xenograft model.
Caused no significant weight loss or apparent toxicity.
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Animal Model:NSG mice (5-week-old female)[2]
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Dosage:0.5 mg/kg
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Administration:i.p.; daily; 9 days
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Result:Significantly reduced tumor luciferase flux in liver, spleen, and bone tissues on days 15, 30, and 45.
Notably reduced tumor cell infiltration in liver and spleen tissues.
Significantly lowered numbers of Ki67-positive proliferative cells and BRD4-positive cells in bone, spleen, and liver tissues compared to controls.
Markedly prolonged mouse survival.
Showed no significant difference in body weight relative to controls.
Chemical Information
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No. CAS 2140289-17-2
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Appearance Solid
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Peso molecular 946.02
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Fòrmula C48H55N11O10
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Color Light yellow to yellow
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SMILES
O=C(C1=NC(NC2=CC(C3CC3)=NN2CC)=C4C(NC5=C4C=C(OC)C(C6=C(C)ON=C6C)=C5)=N1)NCCCOCCOCCOCCCNC7=CC=CC(C(N8C(CC9)C(NC9=O)=O)=O)=C7C8=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Publications (2)
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Journal Impact Factor
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Most Recent
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Structure
PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network. [Abstract]2024 Dec 5;32(12):2352-2363.e8. PMID: 39389062 -
Biochem Biophys Res Commun
Accelerating PROTAC drug discovery: Establishing a relationship between ubiquitination and target protein degradation. [Abstract]2022 Nov 5:628:68-75. PMID: 36084553
Solvente y solubilidad
In Vitro:
DMSO : 200 mg/mL (211.41 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 (stored under nitrogen). 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 (stored under nitrogen). 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)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (284 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
[1].
Bai L, et al. Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer. Cancer Res. 2017 May 1;77(9):2476-2487.
[Content Brief]
[2]. Ge H, et al. The BET degrader BETd-246 demonstrated significant anti-tumor efficacy in T-cell acute lymphoblastic leukemia by inhibiting TRAT1. Experimental cell research. 2025 Dec 01;453(2):114791. [Content Brief]
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 (stored under nitrogen). 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 | 1.0571 mL | 5.2853 mL | 10.5706 mL | 26.4265 mL |
| 5 mM | 0.2114 mL | 1.0571 mL | 2.1141 mL | 5.2853 mL | |
| 10 mM | 0.1057 mL | 0.5285 mL | 1.0571 mL | 2.6427 mL | |
| 15 mM | 0.0705 mL | 0.3524 mL | 0.7047 mL | 1.7618 mL | |
| 20 mM | 0.0529 mL | 0.2643 mL | 0.5285 mL | 1.3213 mL | |
| 25 mM | 0.0423 mL | 0.2114 mL | 0.4228 mL | 1.0571 mL | |
| 30 mM | 0.0352 mL | 0.1762 mL | 0.3524 mL | 0.8809 mL | |
| 40 mM | 0.0264 mL | 0.1321 mL | 0.2643 mL | 0.6607 mL | |
| 50 mM | 0.0211 mL | 0.1057 mL | 0.2114 mL | 0.5285 mL | |
| 60 mM | 0.0176 mL | 0.0881 mL | 0.1762 mL | 0.4404 mL | |
| 80 mM | 0.0132 mL | 0.0661 mL | 0.1321 mL | 0.3303 mL | |
| 100 mM | 0.0106 mL | 0.0529 mL | 0.1057 mL | 0.2643 mL |
BETd-246 Related Classifications
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