化学论文翻译 - 英文原文+汉语翻译.pdf

SCIENCE CHINA Chemistry • REVIEWS • October 2013 Vol.56 No.10: 1392–1401 · SPECIAL TOPIC · Chemistry for Life Sciences doi: 10.1007/s11426-013-4963-0 Diversity evolution and jump of Polo-like kinase 1 inhibitors * LIAO Chenzhong YAO RiSheng School of Medical Engineering, Hefei University of Technology, Hefei 230009, China Received April 29, 2013; accepted June 23, 2013; published online August 21, 2013 Polo-like kinase 1 (Plk1), a member of a family of serine/threonine kinases, is an attractive target for the development of anti- cancer drugs because it is involved in the regulation of cell-cycle progression and cytokinesis. This kinase provides two pock- ets for developing Plk1 inhibitors: the N-terminal catalytic domain (NCD) and the polo-box domain (PBD). For both of the two pockets, some natural products were identified as Plk1 inhibitors and some synthetic Plk1 inhibitors were developed by mimicking ATP and phosphopeptides, natural products binding to NCD and PBD respectively. This article not only reviews the progression of Plk1 inhibitors binding to these two pockets, but also discusses diversity evolution and jump in the process of drug development using Plk1 inhibitors as examples and how they impact on drug design and pharmacophore modeling. diversity evolution, diversity jump, Polo-like kinase 1, ATP mimics, natural product 1 Introduction