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HC278 | HC278 : Degrader (PROTAC) of TEAD1, TEAD3
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (0 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
TEAD1
  • Activity:aorund 1 µM
  • Dmax:50%
TEAD3
  • Activity:around 1 µM
    Degrader (PROTAC)
    up to 50 nM
    up to 1 µM

    Selectivity

    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    Unbiased global proteomic analysis was performed on treated NCI-H226 cells with either DMSO or 500 n ...

    Potency
    Cellular
    In Vitro

    TEAD1

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1016/j.heliyon.2024.e37829

    TEAD3

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1016/j.heliyon.2024.e37829

    Negative Control Compounds

    canSAR7437540
    Notes: Negative control HC278-Neg1, in which the TEAD binding warhead is the enantiomer of the one in HC278, exhibited a much weaker degradative effect
    canSAR7437564
    Notes: HC278-Neg2, uses the same warhead as in HC278 but contains an altered CRBN ligand that cannot engage with CRBN, failed to induce degradation of the TEAD proteins

    Chemical Information

    Molecular Formula C43H39F3N6O5
    SMILEs C[C@H](NC(=O)c1ccc2c(Oc3ccc(C(F)(F)F)cc3)cccc2c1)c1cccc(CN2CCN(c3ccc4c(c3)CN(C3CCC(=O)NC3=O)C4=O)CC2)n1
    InChI InChI=1S/C43H39F3N6O5/c1-26(47-40(54)28-8-14-34-27(22-28)4-2-7-38(34)57-33-12-9-30(10-13-33)43(44,45)46)36-6-3-5-31(48-36)25-50-18-20-51(21-19-50)32-11-15-35-29(23-32)24-52(42(35)56)37-16-17-39(53)49-41(37)55/h2-15,22-23,26,37H,16-21,24-25H2,1H3,(H,47,54)(H,49,53,55)/t26-,37?/m0/s1
    Molecular weight 776.29 Da
    AlogP 6.62010000000001
    HBond acceptors 11
    HBond donors 2
    Atoms 96

    References

    Publications

    Cross References

    Expert Reviews

    by SERP
    (on 21 Oct 2024 )
    Cellular Use Rating
    Note that optimal concentrations can be dependent on the assayed cell type and should be tested.
    by SERP
    (on 6 Dec 2024 )
    Cellular Use Rating
    This compound could be used to probe TEAD1/3 biology in cells but with a lot of care. 1) The concentration should be kept at or below 50 nM; based on the data presented in the 10.1016/j.heliyon.2024.e37829...
    by SERP
    (on 20 Feb 2025 )
    Cellular Use Rating
    HC278 can be used as a dual-selective degrader of TEAD1 & TEAD3. At higher concentrations (>500nM) degradation of TEAD-family members TEAD 2 & 4 can also be seen. HC278-Neg2 is recommended as a suitable...
    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