dBET6 |
رقم الكتالوجGC32719
One-Click Copy Product Info
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dBET6 عبارة عن بروتين PROTAC شديد الفعالية وانتقائي وقابل للنفاذ للخلايا متصل بواسطة روابط لـ Cereblon و BET ، مع IC 50 من 14 نانومتر ، وله نشاط مضاد للأورام
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1950634-92-0
Sample solution is provided at 25 µL, 10mM.
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dBET6 is a novel, orally active BRD4 degrader that suppresses the transcription and expression of oncogenes such as c-Myc[1-2]. dBET6 can be used in research related to cancers such as acute myeloid leukemia[3-4].
In vitro, when chronic myeloid leukemia cells (KU812, K562, KCL22, and KCL22T315I) were treated with dBET6 (1nM–50μM) for 48 hours, dBET6 significantly inhibited cell proliferation, induced apoptosis, and blocked MYC expression. dBET6 also synergized with BCR::ABL1 tyrosine kinase inhibitors to overcome drug resistance[5]. When various acute myeloid leukemia and acute lymphoblastic leukemia cell lines (KG1, HL60, MOLM-13, MV4-11, BV-173, NALM-1, etc.) and primary patient-derived AML and ALL cells were treated with dBET6 (0.05μM to 1μM) for 0 to 48 hours. dBET6 significantly inhibited cell growth and viability and induced apoptosis. Additionally, dBET6 overcame osteoblast-induced chemotherapy resistance and suppressed interferon-gamma and tumor necrosis factor-alpha-induced PD-L1 checkpoint antigen expression[6].
In vivo, in a light-induced retinal degeneration model, BALB/cJ and C57BL/6J mice received intraperitoneal injections of dBET6 (10mg/kg) once one hour before light exposure and again 24 hours after exposure. dBET6 significantly improved retinal function and visual sensitivity, inhibited light damage-induced retinal thinning, photoreceptor cell death, and microglia/macrophage activation, and reduced cGAS-STING pathway activity[7]. In a T-ALL xenograft mouse model, dBET6 (7.5mg/kg; intraperitoneal injection twice daily) was administered continuously for 14–18 days. dBET6 significantly reduced the leukemia burden and prolonged survival in the mice[8].
References:
[1] Winter GE, Mayer A, Buckley DL, et al. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. Mol Cell. 2017 Jul 6;67(1):5-18.e19.
[2] Bauer K, Berghoff AS, Preusser M, et al. Degradation of BRD4 - a promising treatment approach not only for hematologic but also for solid cancer. Am J Cancer Res. 2021 Feb 1;11(2):530-545.
[3] Chen Z, Feng Z, Wang S, et al. Engineering Metal-Organic-Framework-Based STING Nanoagonists for PROTAC-Enhanced Cancer Chemo-Metalloimmunotherapy. Adv Sci (Weinh). 2026 Jan;13(2):e15006.
[4] Yu H, Zhao J, Wu D, et al. Exosome encapsulated albumin nanoparticles target delivery of DBET6 as a treatment for triple-negative breast cancer. PLoS One. 2026 Jan 12;21(1):e0335890.
[5] Peter B, Eisenwort G, Sadovnik I, et al. BRD4 degradation blocks expression of MYC and multiple forms of stem cell resistance in Ph+ chronic myeloid leukemia. Am J Hematol. 2022 Sep;97(9):1215-1225.
[6] Bauer K, Hauswirth A, Gleixner KV, et al. BRD4 degraders may effectively counteract therapeutic resistance of leukemic stem cells in AML and ALL. Am J Hematol. 2024 Sep;99(9):1721-1731.
[7] Zhu X, Liu W, Tang X, et al. The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage. J Neuroinflammation. 2023 May 22;20(1):119.
[8] Xu L, Chen Y, Mayakonda A, et al. Targetable BET proteins- and E2F1-dependent transcriptional program maintains the malignancy of glioblastoma. Proc Natl Acad Sci U S A. 2018 May 29;115(22):E5086-E5095.
| Cell experiment [1]: | |
Cell lines | Primary chronic myeloid leukemia (CML) cells, CML cell lines (KU812, K562, KCL22, KCL22T315I), and primary CML leukemic stem cells (LSC; CD34+/CD38-) |
Preparation Method | Primary CML mononuclear cells (MNC) and CML cell lines were cultured in appropriate medium. Cells were treated with dBET6 (1nM-50μM) for 48 hours. |
Reaction Conditions | 1nM-50μM; 48 hours |
Applications | dBET6 significantly inhibited proliferation and induced apoptosis in primary CML cells, including those from blast phase (BP) CML and cells harboring the BCR::ABL1 T315I mutation, overcoming resistance to the BET inhibitor JQ1. |
| Animal experiment [2]: | |
Animal models | Nude mice for U87 GBM xenografts |
Preparation Method | dBET6 (7.5mg/kg; intraperitoneal injection; twice daily) was administered continuously for 14-18 days to mice bearing T-ALL xenograft models. |
Dosage form | 7.5mg/kg; intraperitoneal injection; twice daily. |
Applications | dBET6 significantly prolonged murine survival, reduced tumor incidence, and impaired gliomasphere-initiated tumor formation. dBET6 also downregulated BET protein levels in orthotopic GBM xenografts within 2 hours post-i.p. injection. |
References: | |
| Cas No. | 1950634-92-0 | SDF | |
| Canonical SMILES | O=C(NCCCCCCCCNC(COC1=CC=CC(C(N2C(CC3)C(NC3=O)=O)=O)=C1C2=O)=O)C[C@H]4C5=NN=C(C)N5C6=C(C(C)=C(C)S6)C(C7=CC=C(Cl)C=C7)=N4 | ||
| Formula | C42H45ClN8O7S | M.Wt | 841.37 |
| الذوبان | DMSO : ≥ 100 mg/mL (118.85 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.1885 mL | 5.9427 mL | 11.8854 mL |
| 5 mM | 237.7 μL | 1.1885 mL | 2.3771 mL |
| 10 mM | 118.9 μL | 594.3 μL | 1.1885 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)