Potency assay (cells):
In SJSA-1 cells, MI-77301 inhibited cell growth. Comparable results were found in multiple cell lines that express p53.
Target engagement assay (cells):
In SJSA-1 cells, MI-77301 dose-dependently increased MDM2, p21 and PUMA RNA levels (but not p53 RNA levels), p53, p21, and MDM2 protein levels, and led to apoptosis. In multiple other cancer cell lines (leukemia, prostate cancer, colon cancer), the compound had comparable effects on p53 protein expression.