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CFI-400945 | CFI-400945 : ATP competitive inhibitor of PLK4
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
PLK4
  • Ki:0.26 nM
  • EC50 :12.3 nM
ATP competitive
--

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
In radiometric assays, CFI-400945 inhibited 10/290 kinases >50%. IC50s for a subset of kinases were ...
In Cell Selectivity Assessment

Potency: EC50 - AURKA 510 nM, AURKB 102 nM, TRKA 84 nM, TRKB 88 nM, TEK 117 nM

Potency Assay Off-Target:
Negligible activity was detected against FGFRs and ROS.

Potency
Cellular
In Vitro

PLK4

Mode of Action: ATP competitive

Structure-Activity-Relationship data available? No

In Vivo Validations

CD1 nude mice
Dose: 2.4-20 mg/kg
Route of delivery: Oral
Plasma half life: 3.7-4.2 hr
Organ of interest (O): xenograft
Target engagement assay: Indirect: inhibition of substrate phosphorylation in xenograft tissue

Reference: --

Chemical Information

Molecular Formula C33H34N4O3
SMILEs COc1ccc2c(c1)[C@]1(C[C@H]1c1ccc3c(/C=C/c4ccc(CN5C[C@H](C)O[C@H](C)C5)cc4)n[nH]c3c1)C(=O)N2
InChI InChI=1S/C33H34N4O3/c1-20-17-37(18-21(2)40-20)19-23-6-4-22(5-7-23)8-12-29-26-11-9-24(14-31(26)36-35-29)28-16-33(28)27-15-25(39-3)10-13-30(27)34-32(33)38/h4-15,20-21,28H,16-19H2,1-3H3,(H,34,38)(H,35,36)/b12-8+/t20-,21+,28-,33-/m0/s1
Molecular weight 534.26 Da
AlogP 5.7285
HBond acceptors 7
HBond donors 2
Atoms 74

References

Publications

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    Expert Reviews

    by SERP
    (on 10 Jun 2016 )
    Cellular Use Rating
    In Model Organisms
    The compound, like many kinase inhibitors is not selective for its primary target, and as such should not be considered a PLK4 probe. In a small kinase panel (Cancer Cell 2014, 26, 163-176 in the supporting...
    by SERP
    (on 17 Jun 2016 )
    Cellular Use Rating
    In Model Organisms
    Despite being a well-characterized drug candidate, CFI-400945 as a chemical probe for PLK4 suffers from a poor kinome selectivity. While showing good selectivity against the other PLK-family members,...
    by SERP
    (on 20 Jun 2016 )
    Cellular Use Rating
    In Model Organisms
    AURKB is in a similar pathway to PLK4, so at higher dose ranges phenotype may be due in part to AURKB. Users should see the following for more discussion : Polo-like kinase 4 inhibition: a strategy...
    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