Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold
Hardcastle, IR, Ahmed, Shafiq, Atkins, H, Farnie, G, Golding, BT, Griffin, RJ, Guyenne, S, Hutton, C, Kallblad, P, Kemp, SJ, Kitching, MS, Newell, DR, Norbedo, S, Northen, JS, Reid, RJ, Saravanan, K, Willems, HM and Lunec, J (2006) Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold. J Med Chem, 49 (21). pp. 6209-6221.
Full text not available from this repository.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.
Item Type: | Article |
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Subjects: | Sciences |
Divisions: | Faculty of Health Sciences and Wellbeing Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences |
Depositing User: | Paula Normington |
Date Deposited: | 17 Feb 2016 12:39 |
Last Modified: | 18 Dec 2019 15:38 |
URI: | http://sure.sunderland.ac.uk/id/eprint/6014 |
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