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dBET6

Degrader (PROTAC) of BRD4

Structure

Information

  • BRD4
  • Degrader (PROTAC)
  • up to 1 uM
  • Reviewer recommended concentration: 50-100 nM

In Vitro Validations

Uniprot ID: O60885
Target Class: Epigenetic
Target SubClass: Bromodomain
Potency: IC50
Potency Value: 14 nM BRD4
Potency Assay: BRD4 (BD1) AlphaScreen assay
PDB ID for probe-target interaction (3D structure): 6BOY
Structure-activity relationship: yes
Target aliases:
Bromodomain-containing protein 4, HUNK1, BRD4, BRD ...

DOI Reference: 10.1073/pnas.1712363115

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): BromoScan
Probe Selectivity in Vitro:

dBET6 is high selective for binding to BETs over other human bromodomains, as determined by single point screening at 1 uM dBET6 (BromoScan)

Probe Selectivity in Cell:

Expression proteomics in MOLT4 cells

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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

dBET6 is a cell-permeable chemical cereblon-based degrader of BET bromodomain protein (nanomolar degradation of BRD4, BRD3 and BRD2).
dBET6 was well tolerated in 2-weeks mouse in vivo xenograpf model reported in the literature and show antitumor activity.

(last updated: 18 Dec 2020 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

dBET6 is a high-quality and mouse in vivo capable chemical probe for the proteasomal mediated degradation of BRD2, BRD3 and BRD4. Due to the use of a cereblon binder, any phenotypic effects observed should be compared to those with just a cereblon binder (e.g. lenalidomide).

(last updated: 7 Jan 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

High quality probe which has been characterized extensively in vitro and in vivo with demonstrated target engagement via CETSA. Improved cellular potency and target engagement over another BRD4 PROTAC (dBET1) has also been shown so dBET6 is the preferred probe.

(last updated: 7 Jan 2021 )