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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