dBET6 - CAS 1950634-92-0

Novel degrader of BET bromodomain proteins, prompting a collapse of global elongation that phenocopies CDK9 inhibition. dBET6 is a highly potent, selective and cell-permeable degrader of BET based on PROTAC, with an IC50 of 14 nM, and has antitumor activity.

* Please be kindly noted that our services and products can only be used for research to organizations or companies and not intended for any clinical or individuals.

Molecular Formula
Molecular Weight


    • Specification
      • Solubility
        H2O : < 0.1 mg/mL (insoluble); DMSO : ≥ 100 mg/mL (118.85 mM)
        3 years

        2 years

        In solvent
        6 months

        1 month
        Room temperature in continental US; may vary elsewhere
    • Properties
      • InChI Key
        Canonical SMILES
    • Reference Reading
      • 1. Degradation of BRD4 - a promising treatment approach not only for hematologic but also for solid cancer
        Karin Bauer, Anna S Berghoff, Matthias Preusser, Gerwin Heller, Christoph C Zielinski, Peter Valent, Thomas W Grunt Am J Cancer Res. 2021 Feb 1;11(2):530-545.eCollection 2021.
        Bromodomain (BRD) and extra-terminal (BET) proteins are epigenetic readers that regulate gene expression and promote cancer evolution. Pharmacological inactivation of BRD4 has recently been introduced as a promising anti-neoplastic approach that targets MYC oncogene expression. However, resistance against BRD4-targeting drugs has been described. We compared the efficacy of the small-molecule-type BET BRD inhibitor JQ1 with the recently developed BET protein degraders dBET1 and dBET6 in colon, breast, melanoma, ovarian, lung and prostate cancer cell lines. As determined by qPCR, all BRD4 targeting drugs dose-dependently decreased MYC expression, with dBET6 introducing the strongest downregulation of MYC. This correlated with the anti-proliferative activity of these drugs, which was at least one order of magnitude higher for dBET6 (IC50 0.001-0.5 µM) than for dBET1 or JQ1 (IC50 0.5-5 µM). Interestingly, when combined with commonly used cytotoxic therapeutics, dBET6 was found to promote anti-neoplastic effects and to counteract chemoresistance in most cancer cell lines. Moreover, JQ1 and both BET degraders strongly downregulated baseline and interferon-gamma induced expression of the immune checkpoint molecule PD-L1 in all cancer cell lines. Together, our data suggest that dBET6 outperforms first-generation BRD4 targeting drugs like dBET1 and JQ1, and decreases chemoresistance and immune resistance of cancer.
        2. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment
        Georg E Winter, Andreas Mayer, Dennis L Buckley, Michael A Erb, et al. Mol Cell. 2017 Jul 6;67(1):5-18.e19.doi: 10.1016/j.molcel.2017.06.004.Epub 2017 Jun 29.
        Processive elongation of RNA Polymerase II from a proximal promoter paused state is a rate-limiting event in human gene control. A small number of regulatory factors influence transcription elongation on a global scale. Prior research using small-molecule BET bromodomain inhibitors, such as JQ1, linked BRD4 to context-specific elongation at a limited number of genes associated with massive enhancer regions. Here, the mechanistic characterization of an optimized chemical degrader of BET bromodomain proteins, dBET6, led to the unexpected identification of BET proteins as master regulators of global transcription elongation. In contrast to the selective effect of bromodomain inhibition on transcription, BET degradation prompts a collapse of global elongation that phenocopies CDK9 inhibition. Notably, BRD4 loss does not directly affect CDK9 localization. These studies, performed in translational models of T cell leukemia, establish a mechanism-based rationale for the development of BET bromodomain degradation as cancer therapy.
        3. Versatile Nano-PROTAC-Induced Epigenetic Reader Degradation for Efficient Lung Cancer Therapy
        Huan-Tian Zhang, Rui Peng, Sheng Chen, Ao Shen, Lixin Zhao, Wang Tang, Xiao-He Wang, Zhen-Yan Li, Zhen-Gang Zha, Mengmeng Yi, Lingmin Zhang Adv Sci (Weinh). 2022 Oct;9(29):e2202039.doi: 10.1002/advs.202202039.Epub 2022 Aug 21.
        Recent evidence has indicated that overexpression of the epigenetic reader bromodomain-containing protein 4 (BRD4) contributes to a poor prognosis of lung cancers, and the suppression of its expression promotes cell apoptosis and leads to tumor shrinkage. Proteolysis targeting chimera (PROTAC) has recently emerged as a promising therapeutic strategy with the capability to precisely degrade targeted proteins. Herein, a novel style of versatile nano-PROTAC (CREATE (CRV-LLC membrane/DS-PLGA/dBET6)) is developed, which is constructed by using a pH/GSH (glutathione)-responsive polymer (disulfide bond-linked poly(lactic-co-glycolic acid), DS-PLGA) to load BRD4-targeted PROTAC (dBET6), followed by the camouflage with engineered lung cancer cell membranes with dual targeting capability. Notably, CREATE remarkably confers simultaneous targeting ability to lung cancer cells and tumor-associated macrophages (TAMs). The pH/GSH-responsive design improves the release of dBET6 payload from nanoparticles to induce pronounced apoptosis of both cells, which synergistically inhibits tumor growth in both subcutaneous and orthotopic tumor-bearing mouse model. Furthermore, the efficient tumor inhibition is due to the direct elimination of lung cancer cells and TAMs, which remodels the tumor microenvironment. Taken together, the results elucidate the construction of a versatile nano-PROTAC enables to eliminate both lung cancer cells and TAMs, which opens a new avenue for efficient lung cancer therapy via PROTAC.
    • Preparing Stock Solutions
      • ConcentrationVolumeMass1 mg5 mg10 mg
        1 mM1.1885 mL5.9427 mL11.8854 mL
        5 mM0.2377 mL1.1885 mL2.3771 mL
        10 mM0.1189 mL0.5943 mL1.1885 mL
        50 mM0.0238 mL0.1189 mL0.2377 mL
Bio Calculators
Stock concentration: *
Desired final volume: *
Desired concentration: *


* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2

* Total Molecular Weight:
Tip: Chemical formula is case sensitive. C22H30N4O c22h30n40
Related Products
BOC Sciences Support

Please contact us with any specific requirements and we will get back to you as soon as possible.

  • Verification code

We invite you to contact us at or through our contact form above for more information about our services and products.

  • International:
  • US & Canada (Toll free):
  • Email:
  • Fax:
  • Email:
Inquiry Basket