The discovery of nongenotoxic activators of p53: building on a cell-based high-throughput screen.

Autor: McCarthy AR; School of Chemistry and Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife, Scotland, UK. anna.mccarthy@ki.se, Hollick JJ, Westwood NJ
Jazyk: angličtina
Zdroj: Seminars in cancer biology [Semin Cancer Biol] 2010 Feb; Vol. 20 (1), pp. 40-5. Date of Electronic Publication: 2010 Mar 04.
DOI: 10.1016/j.semcancer.2010.02.007
Abstrakt: The reactivation of mutant forms of the transcriptional regulator p53 or artificially raising activated p53 levels in a controlled nongenotoxic manner are seen as two of the grand challenges in anti-cancer drug discovery. Recent reports suggest that these demanding goals are achievable. This review article focuses on the use of cell-based high-throughput screening to discover novel nongenotoxic activators of endogenous p53. This challenging approach to the early phases of drug discovery prioritises the discovery of compounds with activity in cells in the hope that the compounds discovered will ultimately be of more direct relevance to therapeutic development. However, this approach also requires that protein target identification studies are carried out. We, and others, have shown that whilst a sometimes daunting proposition, it is possible to identify the targets of compounds that activate p53.
(Copyright (c) 2010. Published by Elsevier Ltd.)
Databáze: MEDLINE
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