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Nat Rev Drug Discov. 2014 Mar;13(3):217-36. doi: 10.1038/nrd4236.

Drugging the p53 pathway: understanding the route to clinical efficacy.

Author information

1
p53 Laboratory (p53Lab), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #06-06, Immunos, 138648 Singapore.
2
1] Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street #07-01, Matrix, 138671 Singapore. [2] School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore. [3] Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543 Singapore.

Erratum in

  • Nat Rev Drug Discov. 2014 Apr;13(4):314. Hoe, Khoo Kian [corrected to Khoo, Kian Hoe].

Abstract

The tumour suppressor p53 is the most frequently mutated gene in human cancer, with more than half of all human tumours carrying mutations in this particular gene. Intense efforts to develop drugs that could activate or restore the p53 pathway have now reached clinical trials. The first clinical results with inhibitors of MDM2, a negative regulator of p53, have shown efficacy but hint at on-target toxicities. Here, we describe the current state of the development of p53 pathway modulators and new pathway targets that have emerged. The challenge of targeting protein-protein interactions and a fragile mutant transcription factor has stimulated many exciting new approaches to drug discovery.

PMID:
24577402
DOI:
10.1038/nrd4236
[Indexed for MEDLINE]

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