GSK864

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency: 

IC50

R132H IDH1 15 nM

Potency assay: 

R132C IDH1 8.8 nM, R132G IDH1 16.6 nM NADPH production and thermal shift assay

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

5DE1

Off target activity

Potency (off target): 

IC50

Off target protein and potency: 

wild-type IDH1 466.5 nMR140Q IDH2 1916 nMR172S IDH2 997 nMwild-type IDH2 1360 nM

In cell validation

On target activity in cells

Potency in cells: 

EC50

320 nM

Potency assay (cells): 

LC/MS/MS analysis from HT-1080 fibrosarcoma cells

Target engagement assay (cells): 

Indirect: quantification of R-2HG levels

In vivo validation

Organism: 

mice

Dose: 

150 mg/kg

Route of delivery: 

Intraperitoneal

Cmax: 

5830 ng/mL

Organ of Interest

Organ (O): 

bone marrow xenograft

Target engagement assay: 

Indirect: quantification of R-2HG levels