ABBV-744

Inhibitor of BRD2, BRD4, BRD3, BRDT

Structure

Information

  • BRD2
  • BRD4
  • BRD3
  • BRDT
  • Inhibitor
  • up to 100 nM

In Vitro Validations

Uniprot ID: P25440
Target Class: Epigenetic
Target SubClass: Bromodomain
Potency: Ki
Potency Value: 4.6 nM BD2
Potency Assay: TR-FRET
PDB ID for probe-target interaction (3D structure): 6E6J 6ONY
Structure-activity relationship: yes see DOI:10.1038/s41586-020-1930-8
Target aliases:
Bromodomain-containing protein 2, RING3, KIAA9001, ...

DOI Reference: 10.1021/acs.jmedchem.0c00628

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): ABBV-744 potently inhibited the BD2 domain of BET family proteins with more than 290 fold selectivity relative to the BD1 domains of BRD2, BRD3 and BRD4, and more than 95 fold selectivity compared with BD1 of BRDtT using TR-FRET.
Probe Selectivity in Vitro:
ABBV-744 lacked significant activity against 75 kinases and 22 bromodomain-containing proteins that represent diverse branches of the kinome and bromodome
Potency in cells, off target : IC50 BRD2 BD1 2449 nM, BRD4 BD1 2006 nM, BRDt BD1 1835 nM, BRD3 BD3 7501 nM
Potency assay, off target (cells): nanoBRET and TR-FRET
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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 19 May 2020 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

ABBV-744 is an excellent chemical probe for studies on the second bromodomain (BD2) of BET bromodomain proteins. The inhibitor is based on the panBET bromodomain inhibitor ABBV-075 (mivebresib) which I suggest to be used in parallel to study BD2 versus pan BET bromodomain selective effects. Unfortunately, no negative control has been used / characterized in the article by Faivre et al (Nature 578, 306-310). I recommend therefore using other available BET inhibitors of different scaffold in parallel in cell based studies. ABBV-744 is suitable for in vivo use in mice.

(last updated: 4 Jun 2020 )

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 27 Oct 2020 )