Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction

Ian R. Hardcastle, Shafiq U. Ahmed, Helen Atkins, A. Hilary Calvert, Nicola J. Curtin, Gillian Farnie, Bernard T. Golding, Roger J. Griffin, Sabrina Guyenne, Claire Hutton, Per Källblad, Stuart J. Kemp, Martin S. Kitching, David R. Newell, Stefano Norbedo, Julian S. Northen, Rebecca J. Reid, K. Saravanan, Henriëtte M G Willems, John Lunec

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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 μM in an ELISA assay, and induced p53-dependent gene transcription in a dose-dependent manner, in the SJSA human sarcoma cell line. © 2005 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)1515-1520
    Number of pages5
    JournalBioorganic and Medicinal Chemistry Letters
    Volume15
    Issue number5
    DOIs
    Publication statusPublished - 1 Mar 2005

    Keywords

    • Cancer
    • MDM2
    • p53
    • Protein-protein interactions

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