PG3-Oc is a small-molecule that restores p53 pathway-signaling in tumor cells with mutant-p53, activates ATF4 and upregulates p53 target genes, inhibits cell viabiltiy of p53 mutation R273H (HT29 cell) with IC50 of 31 nM.
PG3-Oc inhibits cell proliferation and induces apoptosis in mutant p53-expressing cancer cell lines with IC50 values within the nano-molar range.
PG3-Oc has a 4- to 9-fold therapeutic index in colorectal cancer cell lines as compared to normal colon cells CCD 841 Con.
PG3-Oc treatment induces caspase-8 and caspase-3 activation in CRC cell lines, and caspase activation is required for PG3-Oc-induced cell death.
PG3-Oc partially restores the p53 pathway globally.
PUMA is required for PG3-Oc-mediated cell death, induces significant downregulation of MYC and upregulation of PUMA protein levels in a panel of p53 mutant cell lines, such as HT29, DLD1, FaDu, MDA-MB-231, and MDA-MB-468. SW480 and CAL27.
PG3-Oc induces upregulation of ATF4, ATF4 is a mediator of PG3-Oc-induced p53 pathway restoration.
PG3-Oc (5 mg/kg, times weekly for 2 wk) inhibits tumor growth in the HT29 mouse xenograft model.