Fig. 3. p53 TAD1 binders inhibit p53-MDM2 interaction in cells and activate the p53 pathway in cancer cells in MCF-7. (A) Compounds 1047 and 1050 inhibit p53-MDM2 interaction in the nanoBRET cellular assay. Data presented as mean (n = 3). *P < 0.03, **P < 0.002, ***P < 0.0002 (unpaired two-tailed t-test). (B) Compound 1050 stabilizes p53 and elevates protein levels of p53 target p21 and puma. (C and D) Compound 1047 and 1050 treatment induces dose-dependent expression of p53 target genes in MCF-7 cell line by quantitative PCR. (E and F) Compounds 1047 and 1050 induce cell cycle arrest in MCF-7 cells. Data presented as mean (n = 3). ***P < 0.0002, ****P < 0.0001 (unpaired two-tailed t-test).