Ha Siyoung, Oh Jiwon, Kim Yong-Hak, Ham Seung Wook
Department of Chemistry, Chung-Ang University, Seoul 06974, Republic of Korea.
Department of Catholic, University of Daegu, School of Medicine, Daegu 705-718, Republic of Korea.
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Aug 15;1060:71-75. doi: 10.1016/j.jchromb.2017.05.037. Epub 2017 Jun 3.
Importin β1 (KPBN1) appears to be overexpressed in several cancer cells and siRNA-induced inhibition of KPNB1 shows significant inhibition of cancer cell proliferation, but do not affect normal cells. These results indicate that KPNB1 is a potential target and inhibition of KPNB1 can be used as a novel therapeutic approach for the treatment of cancer. Recently, we identified the aminothiazole derivative 1 as a KPNB1-targeted anticancer agent. Herein, we report that compound 1 binds strongly to KPNB1, in a pocket centered around serine-476, as shown by UV-crosslinking and tandem mass spectrometry experiments, and supported using a model derived from molecular docking.
输入蛋白β1（KPBN1）在几种癌细胞中似乎过度表达，而小干扰RNA诱导的KPNB1抑制显示出对癌细胞增殖的显著抑制作用，但不影响正常细胞。这些结果表明，KPNB1是一个潜在靶点，抑制KPNB1可作为一种新型的癌症治疗方法。最近，我们鉴定出氨基噻唑衍生物1是一种靶向KPNB1的抗癌剂。在此，我们报告化合物1与KPNB1强烈结合，结合位点围绕丝氨酸-476形成一个口袋，这通过紫外线交联和串联质谱实验得到证明，并通过分子对接衍生的模型得到支持。
