GSK789

GSK789 : BD1 selective inhibitor of BRD2, BRD3, BRD4, BRDT

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe GSK789 is in the process of SERP review.

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Information

BRD2
BRD3
BRD4
BRDT

Inhibitor

up to 10 uM

Additional Data

SGC image SGC Chemical Probe Collection

In Vitro Validations

Uniprot ID: P25440

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: IC50

Potency Value: 100 nM

Potency Assay: BET mutant TR-FRET assay (BRD2 BD1)

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Bromodomain-containing protein 2, RING3, KIAA9001, ...

DOI Reference: 10.1021/acs.jmedchem.0c00614

Uniprot ID: P25440

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: Kd

Potency Value: 20 nM

Potency Assay: BRD2 BD1 Bromoscan (DiscoverX)

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Bromodomain-containing protein 2, RING3, KIAA9001, ...

DOI Reference: 10.1021/acs.jmedchem.0c00614

Uniprot ID: P25440

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: Kd

Potency Value: 4 nM

Potency Assay: BRD2 BD1 Chemoproteomics

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Bromodomain-containing protein 2, RING3, KIAA9001, ...

DOI Reference: 10.1021/acs.jmedchem.0c00614

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Selectivity within target family - BROMOScan (DiscoverX) (34 tested): selective for the BD1 domain of BET proteins with the exception of the following two hits: TAF1 BD2 (pKd = 7.3) and TAF1L BD2 (pKd = 6.4). But In house TAF(1) FRET pIC50 = 5.0 ± 0.1, n = 3 (BRD4 BD1 selectivity = 500-fold). Selectivity outside target family - Clean in-house panel (40 targets, data not shown). Clean GPCR scan except for one off-target: DRD4 Ki = 1013.12 nM.

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

SERP+ Comments:

The probe is a potent inhibitor of BD1 of the BET family. It shows 1000 fold selectivity against BD2, and to date it is the only known probe with this selectivity window. Moreover, control and orthogonal compounds are provided. Of particular interest is the control, which is the stereoisomer of the active compound. The configuration of the stereocenter shows a considerable influence on the IC50.

(last updated: 23 Sept 2024 )