| Literature DB >> 17034127 |
Ian R Hardcastle1, Shafiq U Ahmed, Helen Atkins, 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.
Abstract
From a set of weakly potent lead compounds, using in silico screening and small library synthesis, a series of 2-alkyl-3-aryl-3-alkoxyisoindolinones has been identified as inhibitors of the MDM2-p53 interaction. Two of the most potent compounds, 2-benzyl-3-(4-chlorophenyl)-3-(3-hydroxypropoxy)-2,3-dihydroisoindol-1-one (76; IC(50) = 15.9 +/- 0.8 microM) and 3-(4-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxybenzyloxy)-2-propyl-2,3-dihydroisoindol-1-one (79; IC(50) = 5.3 +/- 0.9 microM), induced p53-dependent gene transcription, in a dose-dependent manner, in the MDM2 amplified, SJSA human sarcoma cell line.Entities:
Mesh：
Substances：
Year: 2006 PMID： 17034127 DOI： 10.1021/jm0601194
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446