Affinity-based screening of MDM2/MDMX-p53 interaction inhibitors by chemical array: Identification of novel peptidic inhibitors

作者：Noguchi Taro; Oishi Shinya^*; Honda Kaori; Kondoh Yasumitsu; Saito Tamio; Kubo Tatsuhiko; Kaneda Masato; Ohno Hiroaki; Osada Hiroyuki; Fujii Nobutaka

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(13): 3802-3805.

DOI：10.1016/j.bmcl.2013.04.094

• MDM2
• MDMX
• p53 Protein
• HTS
• Microarray technology

MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibitor candidates by affinity-based screening using a chemical array has been established. A number of compounds from an in-house compound library, which were immobilized onto a chemical array, were screened for interaction with fluorescence-labeled MDM2 and MDMX proteins. The subsequent fluorescent polarization assay identified several compounds that inhibited MDM2-p53 and MDMX-p53 interactions.

• 出版日期2013-7-1