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NSC194598 is a p53 DNA-binding inhibitor with an in vitro IC50 value of 180 nM. NSC194598 selectively inhibited DNA binding by p53 and homologs p63/p73, but did not affect E2F1, TCF1, and c-Myc. Furthermore, NSC194598 suppressed p53 transcriptional output after DNA damage in culture and increased the survival of mice after irradiation.