Pilot screening programme for small molecule activators of p53.
Activation of the p53 tumour suppressor is predicted to have therapeutically beneficial effects. Many current anti-cancer therapies activate the p53 response via DNA damage. Non-genotoxic activation of the p53 pathway would open the way to long-term and possibly prophylactic treatments. We have established a simple protocol to screen small compound libraries for activators of p53-dependent transcription, and to select and characterise the most interesting hits, which include non-genotoxic activators. These compounds or their derivatives are of potential clinical interest. This approach may also lead to the identification of novel p53-activating compound families and possibly to the description of novel molecular pathways regulating p53 activity.
Berkson
Rachel G
RG
Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom.
Hollick
Jonathan J
JJ
Westwood
Nicholas J
NJ
Woods
Julie A
JA
Lane
David P
DP
Lain
Sonia
S
D000818:Animals; D020552:Comet Assay; D004249:DNA Damage; D005347:Fibroblasts; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D017930:Genes, Reporter; D016158:Genes, p53; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53