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GSK973 | GSK973 : BD2 selective inhibitor of BRD2, BRD3, BRD4, BRDT
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
BRD2
  • IC50:32 nM
  • Kd:5 nM
    BRD3
    • IC50:16 nM
    • Kd:3 nM
      BRD4
      • IC50:16 nM
      • Kd:2 nM
      • Kd:34 nM
      • IC50:50 nM
      BRDT
      • IC50:16 nM
      • Kd:5 nM
        Inhibitor
        up to 10 uM

        Selectivity

        In Vitro Selectivity Assessment
        Selectivity Assessment Description:
        Selectivity within target family - BROMOScan (DiscoverX) (34 tested): selective for the BD2 domain o ...

        Potency
        Cellular
        In Vitro

        BRD2

        Mode of Action: Inhibitor

        Structure-Activity-Relationship data available? No

        DOI Reference: 10.1021/acsmedchemlett.0c00247

        BRD3

        Mode of Action: Inhibitor

        Structure-Activity-Relationship data available? No

        DOI Reference: 10.1021/acsmedchemlett.0c00247

        BRD4

        Mode of Action: Inhibitor

        Structure-Activity-Relationship data available? No

        DOI Reference: 10.1021/acsmedchemlett.0c00247

        BRDT

        Mode of Action: Inhibitor

        Structure-Activity-Relationship data available? No

        DOI Reference: 10.1021/acsmedchemlett.0c00247

        In Vivo Validations

        Rat
        Dose: 1 mg/Kg
        Route of delivery: Intravenous
        Plasma half life: 0.6 h
        Systemic clearance: 73 mL/min/kg
        Volume of Distribution at Steady-State: 2.1 L/kg

        DOI Reference: 10.1021/acsmedchemlett.0c00247

        Dose: 3 mg/Kg
        Route of delivery: Oral
        Bioavailability: 48%

        DOI Reference: 10.1021/acsmedchemlett.0c00247

        Dog
        Dose: 1 mg/Kg
        Route of delivery: Intravenous
        Plasma half life: 4.8 h
        Systemic clearance: 3 mL/min/kg
        Area Under the Curve:: 1.3 L/kg

        DOI Reference: 10.1021/acsmedchemlett.0c00247

        Dose: 2 mg/Kg
        Route of delivery: Oral
        Bioavailability: 87%

        DOI Reference: 10.1021/acsmedchemlett.0c00247

        Negative Control Compounds

        GSK943
        Notes: Enantiomer GSK943 BET mutant TR-FRET assay: BRD4 (BD1) pIC50 < 4.3; (BD2) = 5.1, 500-fold Clean GPCR scan except for one off-target: GABAA/BZP (Ki = 473.91 nM).

        Orthogonal Probes def

        GSK620
        GSK046
        ABBV-744

        Chemical Information

        Molecular Formula C23H23FN2O4
        SMILEs CNC(=O)c1cc(C(=O)N[C@@H]2[C@H]3COC[C@H]32)cc2c1O[C@H](CF)[C@H]2c1ccccc1
        InChI InChI=1S/C23H23FN2O4/c1-25-23(28)15-8-13(22(27)26-20-16-10-29-11-17(16)20)7-14-19(12-5-3-2-4-6-12)18(9-24)30-21(14)15/h2-8,16-20H,9-11H2,1H3,(H,25,28)(H,26,27)/t16-,17+,18-,19+,20+/m1/s1
        Molecular weight 410.16 Da
        AlogP 0.0
        HBond acceptors 6
        HBond donors 2
        Atoms 53

        Vendors

        Note: This is not an exhaustive list and does not indicate endorsement by the portal.

        Expert Reviews

        by SERP
        (on 3 Mar 2022 )
        Cellular Use Rating
        In Model Organisms
        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...
        by SERP
        (on 7 Mar 2022 )
        Cellular Use Rating
        In Model Organisms
        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...
        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. Read more about our evaluation criteria