Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 15, Issue 5, Pages 1515-1520Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2004.12.061
Keywords
cancer; MDM2; p53; protein-protein interactions
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A series of 2-N-alkyl-3-aryl-3-alkoxyisoindolinones has been synthesised and evaluated as inhibitors of the MDM2-p53 interaction. The most potent compound, 3-(4-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2,3-dihydroisoindol-1-one (NU8231), exhibited an IC50 of 5.3 +/- 0.9 mu M in an ELISA assay, and induced p53-dependent gene transcription in a dose-dependent manner, in the SJSA human sarcoma cell line. (c) 2005 Elsevier Ltd. All rights reserved.
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