PTC-028 (C09-1017-672)

InformationPTC-028 PTC-028 is an orally bioavailable compound that decreases BMI-1 levels by posttranslational modification.TargetsBMI-1In vitroPTC-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.In vivoorally administered PTC-028, as a single agent, exhibits significant antitumor activity comparable with the standard cisplatin/paclitaxel therapy in an orthotopic mouse model of ovarian cancer. After administration of single oral doses to the CD-1 mice, total plasma AUC0-24h 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.Cell Research(from reference)Cell lines：Immortalized ovarian surface epithelium (OSE) or the fallopian tube epithelium(FTE) cells and ovarian cancer cells Concentrations：0-500 nmol/L Incubation Time：48 h. Specification: 10mM in DMSO Molecular Formula: C19H12F5N5 Molecular Weight: 405.32 PubChem CID: 73427235 Isomeric SMILES: CC1=NC2=CC(=C(C=C2N1C3=NC(=CN=C3)NC4=CC=C(C=C4)C(F)(F)F)F)F