2. Academic Validation
  3. Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction

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

  • Bioorg Med Chem Lett. 2005 Mar 1;15(5):1515-20. doi: 10.1016/j.bmcl.2004.12.061.
Ian R Hardcastle 1,  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
Affiliations

Affiliation

  • 1 Northern Institute for Cancer Research, School of Natural Sciences-Chemistry, Bedson Building, University of Newcastle upon Tyne, Newcastle upon Tyne, NE1 7RU, UK. i.r.hardcastle@ncl.ac.uk
PMID: 15713419 DOI: 10.1016/j.bmcl.2004.12.061
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 microM in an ELISA assay, and induced p53-dependent gene transcription in a dose-dependent manner, in the SJSA human sarcoma cell line.

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