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Chemical Structure| 1950634-92-0 Chemical Structure| 1950634-92-0

Structure of dBET6
CAS No.: 1950634-92-0

Chemical Structure| 1950634-92-0

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dBET6 is a highly potent, selective, and cell-permeable PROTAC that targets Cereblon and BET, with an IC50 of 14 nM, demonstrating antitumor activity.

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Product Details of dBET6

CAS No. :1950634-92-0
Formula : C42H45ClN8O7S
M.W : 841.37
SMILES Code : 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
MDL No. :MFCD31692407
InChI Key :JGQPZPLJOBHHBK-UFXYQILXSA-N
Pubchem ID :121427831

Safety of dBET6

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of dBET6

epigenetics

Isoform Comparison

Biological Activity

Target
  • BET

    BRD4, IC50:14 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MOLT4 100 nM 2 hours To evaluate the effect of dBET6 on BRD4 degradation PMC5663500
U87 GBM cells 1 μM 2 hours DBET6 degraded BRD2, BRD3, and BRD4 via CRBN-dependent proteasomal pathway. PMC5984485
U87 GBM cells 0.5 μM 24 hours DBET6 inhibited phosphorylation of RNA-Pol2. PMC5984485
NCI-H1963 300 nM 4 and 8 hours DBET6 treatment significantly reduced the mRNA levels of ASXL3 PMC7362484
293FTWT 100 nM 4 hours To evaluate the effect of dBET6 on BRD4 degradation PMC5663500
661W cells 100 nM 2 hours To evaluate the effect of dBET6 on BRD4 protein levels in 661W cells. Results showed that dBET6 decreased BRD4 protein levels in a dose-dependent manner. PMC10201800
DLD-1 cells 250 nM 2 hours and 24 hours Leads to degradation of all BET proteins, mimicking increased Pol II promoter-proximal pausing due to BRD4 loss and reduced enhancer activity due to BRD2 loss PMC7849361
Lewis lung carcinoma cells (LLC cells) 7.5 µg/mL 24 hours To evaluate the cytotoxicity and apoptosis-inducing effects of RLDPB on LLC cells. Results showed that RLDPB significantly induced apoptosis (~95%) and inhibited tumor cell proliferation by degrading BRD4 and activating the Caspase-3 pathway. PMC11552110
NNI-24 tumor spheres 50 nM 24 hours DBET6 exerted a potent antiproliferative activity against GBM spheres and mitigated their sphere-forming efficiency. PMC5984485
BV2 cells 50 nM 24 hours To evaluate the effect of dBET6 on BRD4 protein levels in BV2 cells. Results showed that dBET6 significantly repressed LPS/IFNγ-induced pro-inflammatory factor expression, such as IL1β, TNF and IL6. PMC10201800
Prostate cancer cells (DU-145, LNCAP) 0.001-5 µM 48 hours DBET6 showed the strongest anti-proliferative and pro-apoptotic effects in prostate cancer cells PMC7868748
Lung cancer cells (H1993, H2073) 0.001-5 µM 48 hours DBET6 significantly inhibited lung cancer cell proliferation and enhanced the effects of chemotherapeutic drugs PMC7868748
Ovarian cancer cells (A2780, HEY, SKOV3) 0.001-5 µM 48 hours DBET6 showed the strongest anti-proliferative and pro-apoptotic effects in ovarian cancer cells PMC7868748
Melanoma cells (607B, A375, MEL-JUSO) 0.001-5 µM 48 hours DBET6 significantly induced apoptosis in melanoma cells and showed stronger effects at low concentrations PMC7868748
Breast cancer cells (MCF7, SKBR3, T47D) 0.001-5 µM 48 hours DBET6 showed the strongest anti-proliferative activity in breast cancer cells, with significantly lower IC50 values than other drugs PMC7868748
Colon cancer cells (HCT15, HCT116, HT29) 0.001-5 µM 48 hours DBET6 significantly inhibited MYC expression and cell proliferation, with IC50 values lower than dBET1 and JQ1 PMC7868748

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6 mice Subcutaneous and orthotopic Lewis lung carcinoma models Intravenous injection 5 mg/kg Every 2 days for 19 days To evaluate the tumor-suppressive effects of CREATE, results showed that CREATE significantly inhibited tumor growth. PMC9561860
Mice T cell acute lymphoblastic leukemia model Intraperitoneal injection 7.5 mg/kg Twice daily for a total of 18 days To evaluate the in vivo efficacy of dBET6 in T-ALL model PMC5663500
C57BL/6 mice LLC tumor model Intravenous injection 2.5 mg/kg Every 2 days for 18 days To evaluate the anti-tumor effects of RLDPB in vivo. Results showed that RLDPB significantly inhibited tumor growth (tumor volume reduced to ~1/15) and induced tumor cell apoptosis by degrading BRD4 and activating the Caspase-3 pathway. PMC11552110
NSG mice Chronic myeloid leukemia model Tail vein injection 1 μM Single dose, observed for 6 months (CP) or 10 weeks (BP) DBET6 blocks engraftment of CML LSC in NSG mice PMC9546315
Mice Light damage-induced retinal degeneration model Intraperitoneal injection 10 mg/kg Two injections, 24 hours apart To evaluate the protective effects of dBET6 on light damage-induced retinal degeneration. Results showed that dBET6 improved retinal responsiveness and visual acuity, inhibited retinal macrophages/microglia activation, Müller cell gliosis, photoreceptor death and retinal degeneration. PMC10201800

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.19mL

0.24mL

0.12mL

5.94mL

1.19mL

0.59mL

11.89mL

2.38mL

1.19mL

References

 

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