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ACBI2 | ACBI2 : Preferential degrader (PROTAC) of SMARCA2, also degrading SMARCA4
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
SMARCA2
  • Kd:208 nM
  • EC50:172 ± 109 nM
  • EC50:42 ± 2 nM
  • DC50:1 ± 1 nM
  • Dmax:81 ± 7%
  • DC50:13 ± 14 nM
  • Dmax:86 ± 6%
  • EC50:7 ± 4 nM
SMARCA4
    • DC50:32 nM
    Degrader (PROTAC)
    up to 100 nM

    Selectivity

    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    ACBI2 degrades SMARCA2 with a > 30-fold window over SMARCA4 in RKO cells (SMARCA2 DC50 = 1 nM, SMARC ...

    Potency
    Cellular
    In Vitro

    SMARCA2

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1038/s41467-022-33430-6

    SMARCA4

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1038/s41467-022-33430-6

    In Vivo Validations

    Mouse
    Dose: 5 mg/K
    Route of delivery: Intravenous
    Plasma half life: 3.8 h (MRT)
    Systemic clearance: 2 mL/min/Kg
    Area Under the Curve:: 38000 nM*h
    Volume of Distribution at Steady-State: 0.47 L/Kg

    DOI Reference: 10.1038/s41467-022-33430-6

    Dose: 30 mg/Kg
    Route of delivery: Oral
    Plasma half life: 6.1 h (MRT)
    Area Under the Curve:: 50000 nM*h
    Bioavailability: 22%

    DOI Reference: 10.1038/s41467-022-33430-6

    Negative Control Compounds

    canSAR7437538
    Notes: cis-ACBI2 (cpd 12) is not capable of binding VHL

    Chemical Information

    Molecular Formula C56H68BrFN8O5S
    SMILEs Cc1ncsc1-c1ccc([C@H](CC[C@H](C)CCN2CCC(c3ccc4c(c3)n(C3CCCC3)c3nc(=O)c5c(Br)cccc5n43)CC2)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2(F)CC2)C(C)(C)C)cc1
    InChI InChI=1S/C56H68BrFN8O5S/c1-33(21-26-63-27-22-35(23-28-63)38-18-20-43-45(29-38)65(39-9-6-7-10-39)54-62-51(69)47-41(57)11-8-12-44(47)66(43)54)13-19-42(36-14-16-37(17-15-36)48-34(2)59-32-72-48)60-50(68)46-30-40(67)31-64(46)52(70)49(55(3,4)5)61-53(71)56(58)24-25-56/h8,11-12,14-18,20,29,32-33,35,39-40,42,46,49,67H,6-7,9-10,13,19,21-28,30-31H2,1-5H3,(H,60,68)(H,61,71)/t33-,40+,42-,46-,49+/m0/s1
    Molecular weight 1062.42 Da
    AlogP 9.95002
    HBond acceptors 13
    HBond donors 3
    Atoms 140

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    Expert Reviews

    by SERP
    (on 10 Dec 2024 )
    Cellular Use Rating
    In Model Organisms
    Note should be taken that the oral dose shown above is for PK studies only. In the manuscript, efficacy and tolerability in a xenograft model at a dose of 80 mg/kg are shown, presumably to achieve more...
    by SERP
    (on 23 Dec 2024 )
    Cellular Use Rating
    In Model Organisms
    While ACBI2 should be considered a high quality degrader of SMARCA2 in cells, the use of this tool requires caution. The authors show that 2/4 selectivity can vary widely between cell lines and thus time...
    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