Targeting the Nuclear Transport Machinery by Rational Drug Design
Targeting the Nuclear Transport Machinery by Rational Drug Design
复制标题
通过合理的药物设计瞄准核运输机制
DOI：
10.2174/1381612811319120018
复制
发表时间：
2013-04-01
影响因子：
3.1
通讯作者：
Yang, Yongliang
中科院分区：
文献类型：
--
作者：
Mao, Lei;Yang, Yongliang
CRM1（也称为 Exportin1 或 Xpo1）是核转运受体 importin β 超家族的关键成员。近年来，其作为治疗靶点的潜力引起了人们的广泛关注。 CRM1 控制多种生长调节蛋白和肿瘤抑制蛋白的转运，包括 p53、p21、FOXO、PI3K/AKT、Wnt/β-catenin、AP-1 和 NF-kB 等。CRM1 的过度表达已被发现与多种肿瘤疾病（如胰腺癌和肝癌）相关。此外，CRM1可以介导病毒蛋白的运输，例如Rev，一种HIV复制的必需因子蛋白。此外，CRM1 与细胞周期中有丝分裂的关键步骤有关。近年来，深入的生物学研究使CRM1成为一个有前景的临床靶点。 CRM1介导的转运机制的干扰可以有效治疗多种与细胞增殖相关的人类疾病。本文旨在总结近30年来CRM1抑制剂的研究进展。更重要的是，我们希望从分子模拟的角度为CRM1药物设计提供新的见解。
CRM1 (also referred as exportin1 or Xpo1) is a key member of the importin beta superfamily of nuclear transport receptors. Its potential as therapeutic target has attracted significant attention in recent years. CRM1 controls the transport of a number of growth regulatory proteins and tumor suppressor proteins including p53, p21, FOXO, PI3K/AKT, Wnt/beta-catenin, AP-1 and NF-kB etc. The overexpression of CRM1 has been found to correlate with a variety of neoplastic conditions such as pancreatic and liver cancer. In addition, CRM1 could mediate the transport of viral proteins such as Rev, an essential factor protein for HIV replication. Moreover, CRM1 has been implicated in key steps of mitosis during cell cycles. Over the past years, the in-depth biological studies have rendered CRM1 as a promising clinical target. The interference of CRM1-mediated transport machinery could lead to the effective treatment of a variety of human disease related to cell proliferation. The aim of this paper is to summarize the research progress of CRM1 inhibitors in the late 30 years. More importantly, we want to provide new insights for the CRM1 drug design from the perspective of molecular simulation.