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Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking.

ABSTRACT: NSC 333003 has been identified from the NCI Diversity Set as an inhibitor of the MDM2-p53 protein-protein interaction by in silico docking (virtual screening). Its potency and chemical characteristics render it well suited for lead optimization studies that can result in more potent analogs with improved drug-like properties. Its synthesis was achieved using an acid catalyzed condensation reaction from commercially available benzothiazole hydrazine and pyridyl phenyl ketone in refluxing methanol. Stereochemical implications for this compound are described.

SUBMITTER: Lawrence HR

PROVIDER: S-EPMC2754843 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking.

Lawrence Harshani R HR Li Zhenyu Z Yip M L Richard ML Sung Shen-Shu SS Lawrence Nicholas J NJ McLaughlin Mark L ML McManus Gregory J GJ Zaworotko Michael J MJ Sebti Saïd M SM Chen Jiandong J Guida Wayne C WC

Bioorganic & medicinal chemistry letters 20090503 14

NSC 333003 has been identified from the NCI Diversity Set as an inhibitor of the MDM2-p53 protein-protein interaction by in silico docking (virtual screening). Its potency and chemical characteristics render it well suited for lead optimization studies that can result in more potent analogs with improved drug-like properties. Its synthesis was achieved using an acid catalyzed condensation reaction from commercially available benzothiazole hydrazine and pyridyl phenyl ketone in refluxing methanol ...[more]

PMID: 19457663

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