A small molecule reacts with the p53 somatic mutant Y220C to rescue wild-type thermal stability.

The transcription factor and tumor suppressor protein p53 is the most frequently mutated and inactivated gene in cancer. Mutations in p53 result in deregulated cell proliferation and genomic instability, both hallmarks of cancer. There are currently no therapies available that directly target mutant p53 to rescue wild-type function. In this study we identify covalent compounds that selectively react with the p53 somatic mutant cysteine Y220C and restore wild-type thermal stability.