Pin1 as an anticancer drug target.
Pin1 as an anticancer drug target.
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DOI：
10.1358/dnp.2009.22.7.1381751
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发表时间：
2009-09
影响因子：
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通讯作者：
Guoyan G. Xu;F. Etzkorn
中科院分区：
文献类型：
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作者：
Guoyan G. Xu;F. Etzkorn
Pin 1特异性催化磷酸-Ser/Thr-Pro键的顺式/反式异构化，并通过构象变化对其生物底物的功能的影响在许多细胞事件中起重要作用，包括细胞分裂周期25 C（Cdc 25 C）、c-Jun和p53。Pin 1在许多人类癌症组织中过表达，包括乳腺癌、前列腺癌和肺癌。它的表达与细胞周期蛋白D1水平相关，这有助于细胞转化。Pin 1的过表达促进肿瘤生长，而Pin 1的抑制导致肿瘤细胞凋亡。Pin 1在肿瘤发生中起重要作用，因此可能作为有效的抗癌靶点。已经发现了许多Pin 1的抑制剂，包括几类设计的抑制剂（烯烃电子等排体、还原酰胺、茚满基酮）和天然产物（胡桃醌、pepticinnamin E类似物、PiB及其从文库筛选获得的衍生物）。Pin 1抑制剂可通过阻断细胞周期进程而成为一种新型的抗肿瘤药物。因此，Pin 1代表了一个新的诊断和治疗抗癌药物的目标。
Pin1 specifically catalyzes the cis/trans isomerization of phospho-Ser/Thr-Pro bonds and plays an important role in many cellular events through the effects of conformational change on the function of its biological substrates, including cell division cycle 25 C (Cdc25C), c-Jun and p53. Pin1 is overexpressed in many human cancer tissues, including breast, prostate and lung cancer. Its expression correlates with cyclin D1 levels, which contribute to cell transformation. Overexpression of Pin1 promotes tumor growth, while inhibition of Pin1 causes tumor cell apoptosis. Pin1 plays an important role in oncogenesis and therefore may serve as an effective anticancer target. Many inhibitors of Pin1 have been discovered, including several classes of designed inhibitors (alkene isosteres, reduced amides, indanyl ketones) and natural products (juglone, pepticinnamin E analogues, PiB and its derivatives obtained from a library screen). Pin1 inhibitors could be used as a novel type of anticancer drug by blocking cell cycle progression. Therefore, Pin1 represents a new diagnostic and therapeutic anticancer drug target.