中国药理学通报2017，Vol.33Issue(7)：900-904,5.DOI:10.3969/j.issn.1001-1978.2017.07.004
交叉对话信号的分子绝缘——对创新药物设计的思考
Insulation of cross-talk between signalingpathways-inspiration for innovative drug design
摘要
Abstract
Cross-talk of intracellular signaling pathways that share common components (hubs) is organized in form of a bow-tie network topology.Signaling cross-talk is functionally pleiotropic for target genes regulation, resulting in functional redundancy, synergism and antagonism, which should be precisely controlled to prevent signaling 'leaking' or 'spillover'.Thus, the biological system has evolved multiple insulating mechanisms to achieve stimulus-specific response that maintains intracellular homeostasis.The insulation mechanism of signaling cross-talk suggests: (1) the functional duality of cross-talk molecules that determine cell fate requires selectively targeting dysregulated cross-talk molecules while protecting the normal ones from off-target or unintended effects, and we propose them as the targetable cross-talk molecules;(2) cross-talk molecules are usually carried on the macromolecular complex as their functional platforms, thus the structural plasticity of conformational changes at the interaction surface of cross-talk molecules asks for intensive work on the relationship study between drug binding and biological activity, which we propose as the accessible cross-talk molecules.Therefore, signaling cross-talk and its insulation mechanism play instructive leading roles in resolving the bottlenecks of current drug R&D and improve the clinical outcome.关键词
信号转导/交叉对话/信号绝缘/成靶性/药物接近/蛋白动态/药物设计Key words
signaling transduction/signaling cross-talk/signaling insulation/targetability/drug accessibility/protein dynamics/drug design分类
医药卫生引用本文复制引用
陶丽,金凤,王海波,钱亚云,孙云,陆茵,刘延庆..交叉对话信号的分子绝缘——对创新药物设计的思考[J].中国药理学通报,2017,33(7):900-904,5.基金项目
国家自然科学基金资助项目(No 81573656) （No 81573656）
中国博士后科学基金(No 2017M611396) （No 2017M611396）
