NSC 319726 increases growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. NSC319726 is a p53R175 mutant reactivator and is a lead compound for p53-?targeted drug development.
nsc 319726 is a reactivator of mutant p53 with ic50 value of 8nm [1].nsc 319726 belongs to the thiosemicarbazone family. in a mouse fibroblast cell line balb/c 3t3, nsc 319726 shows greater inhibition of cell growth in cells expressing mutant p53 than in wt p53 control. nsc 319726 is also nontoxic to wi38 human fibroblasts (p53 wt). in three different ovarian carcinoma cell lines (tov112d (p53r175h), ovcar3 (p53r248w) and skov3 (p53-/-)), treatment of nsc 319726 results in an induction of apoptosis in the p53r175 mutant. nsc 319726 restores p53 function through inducing a conformation change of mutant p53 to a “wt-like” structure which can be recognized by the wt specific antibody. the inhibition of cell growth caused by nsc 319726 is also found in the tov112d (p53r175h) xenografts when the dose of nsc 319726 is 1mg/kg. furthermore, it is shown that zinc ion chelation and ros changes are important for the apoptosis induced by nsc319726 [1].
[1] yu x, vazquez a, levine aj, carpizo dr. allele-specific p53 mutant reactivation. cancer cell. 2012 may 15;21(5):614-25.
