CFI-400945

ATP-competitive inhibitor of PLK4

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

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.

Information

PLK4

ATP-competitive inhibitor

Probe Availability:

In Vitro Validations

Uniprot ID: O00444

Target Class: Protein kinase

Target SubClass: Other

Potency: Ki

Potency Value: 0.26 nM

Potency Assay: In vitro kinase assay IC50 = 2.8 nM

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Serine/threonine-protein kinase PLK4, STK18, SAK, ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): In radiometric assays, CFI-400945 inhibited 10/290 kinases >50%. IC50s for a subset of kinases were determined and only 11 were < 100 nM (including ABL, AURKB, BMX, FGFR1, FGFR2, ROS, TEK, TRKA, TRKB).

Potency in cells, off target : EC50 AURKA 510 nM, AURKB 102 nM, TRKA 84 nM, TRKB 88 nM, TEK 117 nM

Potency assay, off target (cells): Negligible activity was detected against FGFRs and ROS.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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 information), there are 4 kinases within 10-fold activity of the potency of this compound for PLK4 in cellular assays.

(last updated: 10 Jun 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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, this compound has some critical off-targets, most importantly AURKB. This kinase also has a crucial role in the cell cycle, and even the authors of the original publication attribute some of the effects observed in cell experiments to the additional inhibition of AURKB.

(last updated: 17 Jun 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

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 for cancer therapy? Holland AJ, Cleveland DW. Cancer Cell. 2014 Aug 11;26(2):151-3. doi: 10.1016/j.ccr.2014.07.017. PMID:25117704

(last updated: 20 Jun 2016 )