GSK973

GSK973 : BD2 selective inhibitor of BRD2, BRD3, BRD4, BRDT

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Probe GSK973 is in the process of SERP review.

Please continue to check back for new reviews and commentary.

Information

BRD2
BRD3
BRD4
BRDT

Inhibitor

up to 10 uM

Additional Data

SGC image SGC Chemical Probe Collection

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: P25440

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: IC50

Potency Value: 32 nM

Potency Assay: BET mutant TR-FRET assay (BRD2 BD2)

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

Target aliases:

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

DOI Reference: 10.1021/acsmedchemlett.0c00247

Uniprot ID: P25440

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: Kd

Potency Value: 5 nM

Potency Assay: BRD2 BD2 Bromoscan (DiscoverX)

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

Target aliases:

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

DOI Reference: 10.1021/acsmedchemlett.0c00247

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Selectivity within target family - BROMOScan (DiscoverX) (34 tested): selective for the BD2 domain of BET proteins; closest hits: TAF1 BD2 (pKd = 6.4), TAF1L BD2 (pKd = 5.7), BRD9 (pKd = 5.7), CECR2 (pKd = 5.5), BAZ2A (pKd = 5.5) and BAZ2B (pKd = 5.1). Selectivity outside target family - Selectivity screen (48 targets tested): clean. Chemoproteomics data (3 vectors) showed excellent non BCPs selectivity. Off-targets in the GPCR scan are DRD3 Ki = 257.47 nM, DRD4 Ki = 982.65 nM and DRD2 Ki = 964.05 nM.

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The bromodomain probe space is heavily populated and these tools add to an already flourishing probeset. However, the active probe is complemented by a very close inactive analogue, to allow matched studies as confirmation of on-target mechanism of action. Use of both tool compounds, plus an additional inhibitor from a different chemotype, will help offset concerns around off-target activity, making thee probes a useful addition to the currently available tools.

(last updated: 3 Mar 2022 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

GSK973 is a potent and selective inhibitor of BET protein BD2 domains suitable for cell-based and in vivo studies in rat and dog, with a bespoke formulation reported for oral exposure in the dog. The enantiomer of GSK973 is reported as a structurally matched negative control. In vivo mouse pharmacokinetics would need to be performed to assess the suitability of GSK973 for interrogating BET BD2 pharmacology in mouse models.

(last updated: 7 Mar 2022 )