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  • Title: Discovery of benzenesulfonamide derivatives as potent PI3K/mTOR dual inhibitors with in vivo efficacies against hepatocellular carcinoma.
    Author: Chen Y, Zhang L, Yang C, Han J, Wang C, Zheng C, Zhou Y, Lv J, Song Y, Zhu J.
    Journal: Bioorg Med Chem; 2016 Mar 01; 24(5):957-66. PubMed ID: 26819001.
    Abstract:
    The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is related to cellular activities. Abnormalities of this signaling pathway were discovered in various cancers, including hepatocellular carcinoma (HCC). The PI3K/mTOR dual inhibitors were proposed to have enhanced antitumor efficacies by targeting multiple points of the signaling pathway. We synthesized a series of propynyl-substituted benzenesulfonamide derivatives as PI3K/mTOR dual inhibitors. Compound 7k (NSC781406) was identified as a highly potent dual inhibitor, which exhibited potent tumor growth inhibition in the hepatocellular carcinoma BEL-7404 xenograft model. Compound 7k may be a potential therapeutic drug candidate for HCC.
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