Table 1.

Inhibitors of the Hdm2:p53 interaction selectively block proliferation of wt p53 tumor cell lines

IC50 (μmol/L), mean ± SE
TDP222669TDP521252
wt p53
    MCF733.3 ± 17.510.0 ± 2.0
    A37546.5 ± 12.012.0 ± 3.5
    HepG245.5 ± 10.811.0 ± 3.7
    A49847.7 ± 10.813.0 ± 1.9
    HCT11658.0 ± 3.014.8 ± 1.5
    LNCaPND4.7 ± 1.5
    ZR75-1ND19.0 ± 6.0
    JAR*33.8 ± 3.619.0 ± 3.7
    SJSA*ND13.8 ± 2.6
    JEG3*ND46.5 ± 6.1
Mutant/null p53
    MDA-MB-231 (mutant)132.1 ± 16.769.7 ±16.2
    Panc1 (mutant)>200>200
    SK-BR-3 (mutant)ND30.5 ± 3.8
    DU145 (mutant)ND66.5 ± 22.4
    MiaPaCa (mutant)>200141.7 ± 7.6
    A431 (mutant)>200123.8 ± 37.9
    PC3 (null)ND41.5 ± 9.3
    SK-OV-3 (null)ND69.8 ± 6.2
    H1299 (null)183.3 ± 28.9101.3 ± 62.4
  • NOTE: Cells were seeded at 1,000 per well in 96-well plates and allowed to adhere overnight. Cells were then exposed to compound dilutions (1.56–100 μmol/L for wt p53 and 3.125–200 μmol/L for mutant and null p53 cell lines) for 72 hours. Six hours before fixation and processing according to the manufacturer's specifications, cells were labeled with bromodeoxyuridine. Prism software was used to calculate the IC50s (mean ± SE) of three separate experiments, each condition done in triplicate.

  • * Cells overexpressing Hdm2.