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Small molecule activators of the p53 response
Marcus J. G. W. Ladds 1,2,* and Sonia Laı´n 1,2,*
1 Department of Microbiology, Tumor and Cell Biology, Biomedicum, Solnava¨gen 9, Karolinska Institutet, 17165, Stockholm, Sweden
2 SciLifeLab, Tomtebodava¨gen 23A, 171 65, Solna, Stockholm, Sweden
*Correspondence to:Marcus J.G.W. Ladds, E-mail:; Sonia Laı´n, E-mail:
J Mol Cell Biol, Volume 11, Issue 3, March 2019, Pages 245-254
Keyword: cancer, p53, small molecule, cell biology, cancer therapy
Drugging the p53 pathway has been a goal for both academics and pharmaceutical companies since the designation of p53 as the ‘guardian of the genome’. Through growing understanding of p53 biology, we can see multiple routes for activation of both wild-type p53 function and restoration of mutant p53. In this review, we focus on small molecules that activate wild-type p53 and that do so in a non-genotoxic manner. In particular, we will describe potential approaches to targeting proteins that alter p53 stability and function through posttranslational modification, affect p53’s subcellular localization, or target RNA synthesis or the synthesis of ribonucleotides. The plethora of pathways for exploitation of p53, as well as the wide-ranging response to p53 activation, makes it an attractive target for anti-cancer therapy.