Molecular Weight(MW): 841.37
dBET6 is a highly cell-permeable degrader of BET bromodomains with an IC50 of 14 nM for BRD4 binding.
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|Description||dBET6 is a highly cell-permeable degrader of BET bromodomains with an IC50 of 14 nM for BRD4 binding.|
dBET6 is a highly cell-permeable degrader of BET bromodomains. It is potent in most cancer cell lines. dBET6 features highly increased cellular potency with evident degradation in the sub-nanomolar range. Treatment with 100 nM dBET6 leads to degradation of BRD4 after 1 hr, prompting subsequent downregulation of c-MYC and induction of apoptosis. dBET6 disrupts global productive transcription elongation. dBET6 treatment leads to a widespread decrease in steady-state mRNA levels, but observed an incommensurate impact on expression of members of the core regulatory circuitry of leukemogenic transcription factors. The collapse of the core transcriptional machinery prompted by BET degradation precedes a robust apoptotic response, of apparent translational significance.
dBET6 is well tolerated. Upon dBET6 treatment, a significant reduction of leukemic burden is observed in a disseminated mouse model of T-ALL. Moreover, mice treated with dBET6 (7.5 mg/kg BID) exhibits a significant survival benefit compared to mice treated with vehicle control or JQ1 (20 mg/kg QD).
|In vitro||DMSO||100 mg/mL (118.85 mM)|
|Ethanol||42 mg/mL (49.91 mM)|
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