GNE-9822

Protein target name:

ITK

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 100 nM

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

HUGO ID:

HGNC:6171

Entrez gene ID:

3702

UNIPROT ID:

Q08881

Target alias:

IL2 inducible T-cell kinase, EMT, LPFS1, LYK, PSCTK2

Probe Details

Chemical Probes Portal ID:

CPP1301

Probe alias:

cpd 28, THI 28, 2W6

PubChem CID:

74983355

ChEMBL ID:

CHEMBL3298371

SMILES string:

O=C(C1=NNC2=C1CCC(C)(C)C2)NC3=CN([C@H](C4=CC=CC=C4)CCN(C)C)N=C3

InChi Key:

XFYUTGIEFKGWND-NRFANRHFSA-N

Physico-chemical properties

Solubility - concentration:

68 uM

NMR:

1H NMR (400 MHz, DMSO) δ 12.78 (s, 1H), 10.05 (s, 1H), 8.08 (s, 1H), 7.66 (s, 1H), 7.37–7.22 (m, 5H), 5.42 (dd, J = 9.3, 5.3, 1H), 2.66 (t, J = 6.0, 2H), 2.38 (s, 2H), 2.25–2.02 (m, 10H), 1.47 (t, J = 6.4, 2H), 0.96 (s, 6H);

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

0.7 nM

Potency assay:

Biochemical Assay

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

4PQN

Structure-activity relationship:

yes

Off target activity

Potency (off target):

Off target protein and potency:

Aurora A

Potency assay (off target):

Aurora A Biochemical Assay

Probe Selectivity in Vitro:

Broad kinase selectivity of this molecule was observed: only six of 286 off-target kinases were inhibited >70% when tested at 0.1 μM (>100X ITK Ki).

In cell validation

On target activity in cells

Potency in cells:

IC50

55 nM

Potency assay (cells):

PLCγ Cellular Assay

In vivo validation

Organism:

MouseRatDog

Dose:

1 IV, 5-50 PO mg/Kg

Route of delivery:

OralIntravenous

Plasma half life:

2.9 (M), 3.0 (R), 5.4 (D) h

Systemic clearance:

40 (M), 70 (R), 21 (D) ml/min/Kg

Cmax:

3.8 (M), 0.2 (R), 0.9 (D) uM

Primary Reference

Reference (doi):

10.1021/jm500550e

Reference (PMID):

24918870

GNE-9822

Probe Information

Target Details

IL2 inducible T-cell kinase, EMT, LPFS1, LYK, PSCTK2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?

Search form

GNE-9822

Probe Information

Target Details

IL2 inducible T-cell kinase, EMT, LPFS1, LYK, PSCTK2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?