Title of article :
1,4-Benzodiazepine-2,5-diones as small molecule antagonists of the HDM2–p53 interaction: discovery and SAR
Author/Authors :
Daniel J. Parks، نويسنده , , Louis V. LaFrance، نويسنده , , Raul R. Calvo، نويسنده , , Karen L. Milkiewicz، نويسنده , , Varsha Gupta، نويسنده , , Jennifer Lattanze، نويسنده , , Kannan Ramachandren، نويسنده , , Theodore E. Carver، نويسنده , , Eugene C. Petrella، نويسنده , , Maxwell D. Cummings، نويسنده , , Diane Maguire، نويسنده , , Bruce L. Grasberger، نويسنده , , Tianbao Lu، نويسنده ,
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.
Keywords :
5-diones , Fluorescence polarization peptide displacement assay , Thermofluor , HDM2 , p53–HDM2 interaction , p53 , 1 , 4-Benzodiazepine-2
