Chemical Probes logo

CFI-402257

CFI-402257 : ATP competitive inhibitor of TTK

Structure

Information

  • TTK
  • Type 1.5 Inhibitor, ATP competitive
  • 10-100 nM

In Vitro Validations

Uniprot ID: P33981
Target Class: Kinase
Target SubClass: Ser/Thr Kinase
Potency: Ki
Potency Value: 0.09 ± 0.02 nM
Potency Assay: TTK Inhibition Assay
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: yes
Target aliases:
Dual specificity protein kinase TTK, MPS1L1, MPS1, ...

DOI Reference: 10.1073/pnas.1700234114

Uniprot ID: P33981
Target Class: Kinase
Target SubClass: Ser/Thr Kinase
Potency: IC50
Potency Value: 1.7 nM
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Dual specificity protein kinase TTK, MPS1L1, MPS1, ...

DOI Reference: 10.1073/pnas.1700234114

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Tested against a panel of human kinases at 1 μM: CFI-402257 inhibited none. The molecule is an intracellular inhibitor of exogenous TTK autophosphorylation with no effect on Aurora kinase A or B or Histone H3 phosphorylation. Outsider target family: CFI-402257 had no activity against CYPs 1A2 and 2D6, inhibited 2C9 and 2C19 with IC50s of 13 and 8 μM, respectively. The level of CYP 3A4 activity reported was substrate dependent with IC50s of 0.51 and 14 μM for BFC and DBF, respectively. CFI-402257 had no activity against CYPs 1A2 and 2D6, inhibited 2C9 and 2C19 with IC50s of 13 and 8 μM, respectively. The level of CYP 3A4 activity reported was substrate dependent with IC50s of 0.51 and 14 μM for BFC and DBF, respectively. Profiled against a panel of 98 nonkinase targets, including G protein-coupled receptors, nuclear receptors, membrane channels, and enzymes @ 10 uM showing only 3 targets with inhibition ≥ 50%.

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This compound appears to be an excellent probe for inhibiting TTK in cells and in mice. Strong structural characterization and biochemical profiling indicate that it is quite selective toward this kinase. The fact that it is highly orally bioavailable and well-tolerated in vivo makes it an attractive probe for this protein. It is now undergoing clinical evaluation in patients with breast cancer.

(last updated: 4 Aug 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

CFI-402257 is a selective inhibitor of Monopolar spindle 1 (Mps1; TTK protein kinase). It is an appropriate chemical probe for assessing the utility of TTK as a novel cancer target.

(last updated: 27 Oct 2021 )