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

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• 作者：Taro Noguchi^a ; Shinya Oishi^a ; ^{soishi@pharm.kyoto-u.ac.jp} ; Kaori Honda^b ; Yasumitsu Kondoh^b ; Tamio Saito^b ; Tatsuhiko Kubo^a ; Masato Kaneda^a ; Hiroaki Ohno^a ; Hiroyuki Osada^b ; Nobutaka Fujii^a ; ^{nfujii@pharm.kyoto-u.ac.jp}
• 关键词：FAM ; carboxyfluorescein ; FP ; fluorescence polarization ; HBTU ; O-(1H-benzotriazol-1-yl)-N ; N ; N&prime ; N&prime ; -tetramethyluronium hexafluorophosphate ; HOBt ; 1-hydroxy-1H-benzotriazole ; MDM2 ; mouse double minute 2 homolog ; MDMX ; mouse double minute X homolog
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 July, 2013
• 年：2013
• 卷：23
• 期：13
• 页码：3802-3805
• 全文大小：972 K

文摘

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.