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- W2572169400 abstract "Non-small cell lung cancer (NSCLC) is a serious life-threatening malignancy. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as Gefitinib and Erlotinib, are effective clinical medicines for advanced NSCLC patients harboring EGFR-activating mutations. However, this therapy just benefits a small percentage of sufferers. Worse still, all patients treated with drugs ultimately develop resistance. Hence, there is still an unmet medical need among patients with NSCLC. In this account, we report a novel multikinase inhibitor SKLB-178, which potently inhibits both EGFR-activating and resistant mutations, as well as the activities of Src and VEGFR2 kinases. SKLB-178 potently inhibited cancer cell growth in both Gefitinib-sensitive and resistant NSCLC cells. Meanwhile, SKLB-178 significantly suppressed the migration, invasion and tube formation of endothelial cells, and the growth of intersegmental vessel in zebrafish. The in vivo pharmacodynamic studies further demonstrated that SKLB-178 had wider potency than Gefitinib, and could significantly prolong survival of animals in A549 experimental metastasis model. These advantages together with the low toxicity of SKLB-178 indicate that SKLB-178 deserves to be further developed as a potential drug candidate for NSCLC therapy." @default.
- W2572169400 created "2017-01-26" @default.
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- W2572169400 date "2017-01-11" @default.
- W2572169400 modified "2023-10-18" @default.
- W2572169400 title "Preclinical pharmacodynamic evaluation of drug candidate SKLB-178 in the treatment of non-small cell lung cancer" @default.
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- W2572169400 doi "https://doi.org/10.18632/oncotarget.14597" @default.
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