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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

Cross References

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Vendors

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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...
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