PTC-028

PTC-028 is an orally bioavailable compound that decreases BMI-1 levels by posttranslational modification. PTC-028 treatment selectively inhibits cancer cells in clonal growth and viability assays, whereas normal cells remain unaffected. Hyperphosphorylation-mediated depletion of cellular BMI-1 by PTC-028 coupled with a concurrent temporal decrease in ATP and a compromised mitochondrial redox balance potentiates caspase-dependent apoptosis^[1].

Cells are treated with PTC-028 at the indicated concentrations for 48 hours and cellular viability is assessed using the MTS assay.

In vivo, orally administered PTC-028, as a single agent, exhibits significant antitumor activity comparable with the standard therapy in an orthotopic mouse model of ovarian cancer. After administration of single oral doses to the CD-1 mice, total plasma AUC_0-24h are 10.9 and 26.1 mg/h/mL at doses of 10 and 20 mg/kg, showing dose proportional pharmacokinetics. The Cmax for PTC-028 at 10 and 20 mg/kg is 0.79 and 1.49 mg/mL, respectively. The Cmax is reached at both dose levels 1-hour postdose after which plasma concentrations slowly reduce^[1].