Empesertib

Protein target name:

TTK

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

100 nM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

Other

HUGO ID:

HGNC:12401

Entrez gene ID:

7272

UNIPROT ID:

P33981

Target alias:

CT96, ESK, MPH1, MPS1, MPS1L1, PYT, TTK

Probe Details

Chemical Probes Portal ID:

CPP1684

Probe alias:

Mps1-IN-5, BAY 1161909, cpd 41, 8QW

PubChem CID:

71599640

ChEMBL ID:

CHEMBL4303241

SMILES string:

C[C@H](C1=CC=C(C=C1)F)C(=O)NC2=CC=C(C=C2)C3=CN4C(=NC(=N4)NC5=C(C=C(C=C5)S(=O)(=O)C)OC)C=C3

InChi Key:

NRJKIOCCERLIDG-GOSISDBHSA-N

Orthogonal probe:

CFI-402257BAY1217389

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

1.7 nM

Potency assay:

HTRF-based MPS1 assay with an ATP concentration of 2 mM

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

6TNB

Structure-activity relationship:

yes

Off target activity

Potency (off target):

% inh.

Off target protein and potency:

JNK2 54% @ 1 uM, JNK3 84% @ 1 uM

Probe Selectivity in Vitro:

Empesertib only inhibits two kinases, JNK2 and JNK3, more than 50% at a concentration of 1 μmol/L and no other kinase at 100 nmol/L in the Millipore kinase panel of 230 kinases

In cell validation

On target activity in cells

Potency in cells:

IC50

53 nM (S), 260 nM (H), 84 nM (K)

Potency assay (cells):

(S) SAC assay: inhibition of the spindle assembly checkpoint was assessed in a high content assay by p-histone H3 staining. (H) Inhibition Cell Proliferation Assay

In vivo validation

Organism:

Mouse, Rat, Dog

Dose:

0.5, 1, 2 mg/Kg

Route of delivery:

OralIntravenous

Plasma half life:

4.9 (M), 14 59 (M), (R), 6.3 (D) h IV

Systemic clearance:

0.69 (M), 0.19 (R), 1.4 (D) L/h/Kg IV

Cmax:

120 (M), 110 (R) ug/L

Tmax:

4 (M, R) h

Primary Reference

Reference (doi):

10.1158/1535-7163.MCT-15-0500 10.1021/acs.jmedchem.9b02035

Reference (PMID):

26832791 32338514

Empesertib

Probe Availability

Probe Information

Target Details

CT96, ESK, MPH1, MPS1, MPS1L1, PYT, TTK

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Empesertib

Probe Availability

Probe Information

Target Details

CT96, ESK, MPH1, MPS1, MPS1L1, PYT, TTK

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?