Synthesis and Biological Evaluation of RGD-Conjugated MEK1/2 Kinase Inhibitors for Integrin-Targeted Cancer Therapy
作者： Xiaoxiao Li , Jianjun Hou , Chao Wang , Xinjie Liu , Hongyan He
DOI: 10.3390/MOLECULES181113957
关键词:
摘要: Abstract: Two novel series of RGD-MEKI conjugates derived from a MEK1/2 kinase inhibitor—PD0325901—have been developed for integrin receptor mediated anticancer therapy. The first series, alkoxylamine analog 9a – g showed anti-proliferation activity in melanoma A375 cells by the same mechanism as that PD0325901. PEGylation increased IC 50 value 9f three-fold assay, and multi-cRGD peptide cargo significantly improved specific 9g integrin-overexpressing U87 cells. In second RGD-PD0325901 13 exhibited antitumor properties compared to analogs both inhibition ERK pathway DNA replication cancer Furthermore, displayed more potent assay than PD0325901 dose-dependent manner. All these data demonstrate with an ester bond linkage enhanced efficacy targeting capability toward tumor
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