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CPI-1612 | Inhibitor of EP300, CREBBP
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 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
EP300
  • IC50:0.5 nM
  • EC 50:14 nM
  • GI 50:7.9 nM
CREBBP
  • IC50:2.9 nM
    Inhibitor
    50 nM for inhibition of H3K18ac (HCT-116), and proliferation of JEKO-1 (sensitive to CBP/EP300 inhibition)
    50 nM

    Selectivity

    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    Eurofins Safety44 off-target screening
    Selectivity Assessment Description:
    Weak activity in a hERG binding assay (IC50 = 10.4 μM) and displayed moderate inhibition of CYP2C8 ( ...

    Potency
    Cellular
    In Vitro

    EP300

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acsmedchemlett.0c00155

    CREBBP

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acsmedchemlett.0c00155

    In Vivo Validations

    Mice , Dog, Rat
    Dose: 1.0 mg/Kg IV, 5.0 mg/Kg PO (M), 0.5 mg/Kg IV, 1.0 mg/Kg PO (D), 1.0 mg/Kg IV, 5.0 mg/Kg PO (R)
    Route of delivery: Intravenous, Oral
    Plasma half life: 5.5 (D), 0.98 (M), 1.2 (R) h
    Systemic clearance: 0.42 (D), 3.8 (M), 2.6 (R) L/h/kg
    Organ of interest (O): Brain
    Target engagement assay: Compound 17 was administered orally to 18 male CD-1 mice. Plasma, brain, and CSF levels of compound 17 were then determined at multiple time points. See the Supporting Information for experimental details and additional data.

    DOI Reference: 10.1021/acsmedchemlett.0c00155

    Negative Control Compounds

    Compound 16

    Orthogonal Probes def

    A-485
    GNE-049

    Chemical Information

    Molecular Formula C27H26N6O
    SMILEs C[C@H](CN[C@@H](C(=O)Nc1ccc(-c2cnn(C)c2)cn1)c1ccccc1)c1ccc(C#N)cc1
    InChI InChI=1S/C27H26N6O/c1-19(21-10-8-20(14-28)9-11-21)15-30-26(22-6-4-3-5-7-22)27(34)32-25-13-12-23(16-29-25)24-17-31-33(2)18-24/h3-13,16-19,26,30H,15H2,1-2H3,(H,29,32,34)/t19-,26-/m1/s1
    Molecular weight 450.22 Da
    AlogP 4.426880000000003
    HBond acceptors 7
    HBond donors 2
    Atoms 60

    References

    Publications

    Cross References

    Vendors

    Note: This is not an exhaustive list and does not indicate endorsement by the portal.

    Expert Reviews

    by SERP
    (on 14 Jul 2020 )
    Cellular Use Rating
    In Model Organisms
    HCT-116 cells are used to measure EC50 on the histone acetylation mark H3K18ac. JEKO-1 are used to measure inhibition of proliferation or GI50. The potency of CPI-1612 aligns in these two assays. In...
    by SERP
    (on 30 Jul 2020 )
    Cellular Use Rating
    In Model Organisms
    CPI-1612 is a probe generated by Constellation Pharma following an extensive hit-to-lead medicinal chemistry campaign designed to optimize the scaffold to obtain an orally active compound against the...
    by SERP
    (on 28 Aug 2020 )
    Cellular Use Rating
    In Model Organisms
    A potent and selective probe that is a good addition to chemical matter for this target. The increase in cellular potency and selectivity make this a welcome addition.
    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