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UNC8209 | UNC8209 : Degrader (PROTAC) of TBK1
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
TBK1
    • DC50:80 ± 20 nM
    • DC50:23 ± 5 nM
    up to 1 uM

    Selectivity

    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    Western Blot of cell lysate
    Selectivity Assessment Description:
    UNC8209 displayed high selectivity for TBK1 degradation over its homolog IKKε, a common off-target o ...
    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    To evaluate the selectivity of UNC8209, global proteomic profiling in UMRC2 cells treated with 1 μM ...
    Selectivity Assessment Description:
    Mass spectrometry analysis identified and quantified 8,307 proteins. Of these, 16 proteins were sign ...

    Potency
    Cellular
    In Vitro

    TBK1

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1016/j.chembiol.2026.03.013

    In Vivo Validations

    Mouse
    Dose: 10 mg/Kg
    Route of delivery: Intraperitoneal
    Cmax: 2300 ng/mL
    Tmax: 2 h

    DOI Reference: 10.1016/j.chembiol.2026.03.013

    Negative Control Compounds

    UNC8461
    Notes: The negative control UNC8461 (NEG) compound failed to reduce TBK1 protein levels.
    SMILES: CN(C(C1CCC1)=O)CCCNC2=NC(NC3=CC=C(OCCOCCOCCOCCOCCOCCCOC4=C5C(C(N(C5=O)C6CCC(N(C)C6=O)=O)=O)=CC=C4)C=C3)=NC=C2Br

    Chemical Information

    Molecular Formula C45H58BrN7O12
    SMILEs CN(CCCNc1nc(Nc2ccc(OCCOCCOCCOCCOCCOCCCOc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)cc2)ncc1Br)C(=O)C1CCC1
    InChI InChI=1S/C45H58BrN7O12/c1-52(42(56)31-6-2-7-31)17-4-16-47-40-35(46)30-48-45(51-40)49-32-10-12-33(13-11-32)64-29-28-63-27-26-62-25-24-61-23-22-60-21-20-59-18-5-19-65-37-9-3-8-34-39(37)44(58)53(43(34)57)36-14-15-38(54)50-41(36)55/h3,8-13,30-31,36H,2,4-7,14-29H2,1H3,(H,50,54,55)(H2,47,48,49,51)
    Molecular weight 967.33 Da
    AlogP 4.375300000000005
    HBond acceptors 19
    HBond donors 3
    Atoms 123

    References

    Publications

    Cross References

    canSAR: 7719231 canSAR: 39

    Expert Reviews

    by SERP
    (on 8 May 2026)
    Cellular Use Rating
    In Model Organisms
    UNC8209 is a potent degrader of TBK1 with a validated PROTAC mechanism of action and improved in vitro selectivity over common off-targets such as IKKƐ. Negative control compound UNC8461 is available....
    by SERP
    (on 27 Jun 2026)
    Cellular Use Rating
    In Model Organisms
    This compound has on and/or off-target inhibition based pharmacology based on the impact of the negative control on cell viability. The paper also shows that it degrades multiple other kinases associated...
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