dBET1

Catalog No.S8296 Batch:S829601

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Technical Data

Formula

C38H37ClN8O7S
Molecular Weight 785.27 CAS No. 1799711-21-9
Solubility (25°C)* In vitro DMSO 100 mg/mL (127.34 mM)
Ethanol 39 mg/mL (49.66 mM)
Water ˂1 mg/mL
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 5.000mg/ml (6.37mM) Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 0.830mg/ml (1.06mM) Taking the 1 mL working solution as an example, add 50 μL of 16.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description dBET1 is a CRBN-based BET degrader with an IC50 of 20 nM, showing high selectivity. Out of 7,429 proteins, only the expression of the oncoproteins MYC and PIM1, as well as BRD2, BRD3 and BRD4 are significantly downregulated by this compound treatment.
Targets
BRD4
20 nM
In vitro

Treatment with dBET1 elicits a comparable, modest effect on MYC and PIM1 expression. Its treatment downregulates MYC and PIM1 transcription, suggestive of secondary transcriptional effects and transcription of BRD4 and BRD3 are unaffected, consistent with post-transcriptional effects. Transcription of BRD2 is affected by this compound and protein stability of the BRD2 gene product is influenced by it. This chemical induces a potent and superior inhibitory effect on MV4;11 cell proliferation at 24 hours (measured by ATP content, IC50 = 0.14 μM). Exposure of primary leukemic patient blasts to this compound elicits dose-proportionate depletion of BRD4 and induction of apoptosis. This compound-mediated targeted degradation of BET proteins robustly dampens pro-inflammatory responses in LPS-stimulated microglia, that is, depletion of BRD2 and BRD4 with it is associated with dramatically reduced LPS-induced COX-2 and iNOS protein levels and pro-inflammatory gene transcription of Nos2, Il-1β, Il-6, Tnfα, Ccl2, Ptgs2, and Mmp9.
In Vivo

Administration of dBET1 attenuates tumour progression and decreases tumour weight assessed post-mortem in murine xenograft model of human MV4;11 leukaemia cells. Pharmacokinetic studies of this compound (50 mg/kg IP) corroborate adequate drug exposure in vivo (Cmax = 392 nM, Tmax=0.5 hr, terminal t1/2=6.69 hr, AUClast=2109 hr*ng/ml, AUCINF=295 hr*ng/ml). Two weeks of this chemical is well tolerated by mice without a meaningful effect on weight, white blood count, haematocrit or platelet count.

Protocol (from reference)

Cell Assay:

[1]
  • Cell Lines

    SUM149 cells

  • Concentrations

    '0.1, 0.5, 1, 5, 10 μM

  • Incubation Time

    18 h

  • Method

    Immunoblot analysis
Animal Study:

[1]
  • Animal Models

    Murine xenograft model of human MV4;11 leukemia cells (CD1 mice)

  • Dosages

    50 mg/kg daily

  • Administration

    i.p.

References

  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937790/
  • https://pubmed.ncbi.nlm.nih.gov/29448097/

Sellecks dBET1 Has Been Cited by 3 Publications

BRD2 protects the rat H9C2 cardiomyocytes from hypoxia‑reoxygenation injury by targeting Nrf2/HO‑1 signaling pathway [ Exp Ther Med, 2023, 10.3892/etm.2023.12241] PubMed: 37869639
BRD2 protects the rat H9C2 cardiomyocytes from hypoxia‑reoxygenation injury by targeting Nrf2/HO‑1 signaling pathway [ Exp Ther Med, 2023, 26(5):542] PubMed: 37869639
Protein Ligand Interactions Using Surface Plasmon Resonance [ Methods Mol Biol, 2021, 2365:3-20] PubMed: 34432236

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.