NSC319726 is a p53(R175) mutant reactivator, exhibits growth inhibition in cells expressing mutant p53, with IC50 of 8 nM for p53(R175) mutant, shows no inhibition for p53 wild-type cells.
NSC319726 is a p53(R175) mutant reactivator, exhibits growth inhibition in cells expressing mutant p53, with IC50 of 8 nM for p53(R175) mutant, shows no inhibition for p53 wild-type cells, shows 10- to 100-fold selectivity over the other hotspot p53 mutants. NSC319276 induces p53(R175)-mutant-dependent apoptosis. NSC319726 treatment induces a WT-like conformational change in the p53(R175) mutant protein that restores sequence-specific p53 transcription. The activity of NSC319726 depends on the zinc ion chelating properties of the compound as well as redox changes.
NSC319726 (5mg/kg, 7days) exhibits greater toxicity for p53(R172H/R172H) mice, with only 30% survival, as compared to 100% survival for p53+/+ and p53-/- mice. NSC319726 inhibits the growth of TOV112D-p53(R175H) xenografts, but not H460 (p53+/+) and MDAMB468-p53(R273W) xenografts. |
