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

Autor:	Shafiq U. Ahmed, Rebecca J. Reid, Roger J. Griffin, Martin S. Kitching, Per Källblad, Stuart J. Kemp, John Lunec, Julian S. Northen, Gillian Farnie, Claire Hutton, Helen Atkins, Ian R. Hardcastle, Bernard T. Golding, Stefano Norbedo, David R. Newell, A. Hilary Calvert, Sabrina Guyenne, Nicola J. Curtin, Henriëtte M. G. Willems, Kappusamy Saravanan
Rok vydání:	2005
Předmět:	Models Molecular Indoles Transcription Genetic Stereochemistry Clinical Biochemistry Pharmaceutical Science Biochemistry Gene product Structure-Activity Relationship Transactivation Transcription (biology) Cell Line Tumor Proto-Oncogene Proteins Drug Discovery Humans Structure–activity relationship Cytotoxicity Molecular Biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Nuclear Proteins Proto-Oncogene Proteins c-mdm2 Molecular biology In vitro Cell culture Docking (molecular) Molecular Medicine Tumor Suppressor Protein p53 Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 15:1515-1520
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2004.12.061
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c6a7cb96a08326b0a364a28e3c377a22 https://doi.org/10.1016/j.bmcl.2004.12.061 Zobrazit plný text záznamu Full Text from ScienceDirect