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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

    Cis-ACBI2
    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...
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