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ID: ALA1140282

Journal: Bioorg Med Chem Lett

Title: 1,4-Benzodiazepine-2,5-diones as small molecule antagonists of the HDM2-p53 interaction: discovery and SAR.

Authors: Parks DJ, Lafrance LV, Calvo RR, Milkiewicz KL, Gupta V, Lattanze J, Ramachandren K, Carver TE, Petrella EC, Cummings MD, Maguire D, Grasberger BL, Lu T.

Abstract: A library of 1,4-benzodiazepine-2,5-diones was screened for binding to the p53-binding domain of HDM2 using Thermofluor, a miniaturized thermal denaturation assay. The hits obtained were shown to bind to HDM2 in the p53-binding pocket using a fluorescence polarization (FP) peptide displacement assay. The potency of the series was optimized, leading to sub-micromolar antagonists of the p53-HDM2 interaction.

CiteXplore: 15664854

DOI: 10.1016/j.bmcl.2004.11.009