MI-888

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency: 

Ki

0.44 nM

Potency assay: 

Fluorescence polarization assay with MDM2 protein and p53 peptide.

Structure-activity relationship: 

Yes, see J Med Chem paper

In cell validation

On target activity in cells

Potency in cells: 

IC50

0.08 uM

Potency assay (cells): 

In SJSA-1 cells, MI-888 dose dependently decreased cell growth.

Target engagement assay (cells): 

In SJSA-1 cells, MI-88 dose-dependently increased expression of p53, MDM2 and p21 proteins.

In vivo validation

Organism: 

Sprague Dawley rat, SCID mice

Dose: 

25 mg/kg (rat)

Route of delivery: 

Oral

Plasma half life: 

3.2 h (rat)

Cmax: 

1,726 ug/L (rat)

Organ of Interest

Organ (O): 

SJSA-1 xenograft (SCID mice, 10-100 mg/kg)

Target engagement assay: 

In xenograft, MI-888 increased expression of p53, MDM2 and p21 proteins.