Novel 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists with improved cellular activity

Bioorganic & Medicinal Chemistry Letters
Kristi A LeonardTianbao Lu

Abstract

The disruption of the p53-Hdm2 protein-protein interaction induces cell growth arrest and apoptosis. We have identified the 1,4-benzodiazepine-2,5-dione scaffold as a suitable template for inhibiting this interaction by binding to the Hdm2 protein. Several compounds have been made with improved potency, solubility, and cell-based activities.

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Citations

Oct 8, 2009·Journal of Combinatorial Chemistry·Aifeng LiuBing Yan
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Jan 1, 2011·MedChemComm·Kareem KhouryAlexander Dömling

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis