基于细胞信号动态网络的药物靶点发现

Drug targets discovery based on dynamic signal transduction networks

药物发现一直以来都集中在寻找疾病过程中某个特定步骤或蛋白质靶点的高特异性的抑制剂上。但是这样高特异性的药物对于如肿瘤、糖尿病、老年痴呆症和神经精神疾病等复杂疾病,治疗效果通常不佳,因此需要重新考虑药物靶点的选择和药物开发的策略。本文将介绍疾病相关的细胞信号转导分子网络及其动态学变化、信号网络的特性及其研究方法,以及构建模型的相关网络资源和工具。重点阐述将信号转导动态网络作为药物靶标的策略方法和过程,包括多靶点药物设计及基于网络的药物研究。

Since last century, drug discovery efforts mostly focus on searching for chemicals which can inhibit some specific steps in a well-described disease pathway. However, this kind of highly specific inhibitors can not be effective for complex diseases, like cancer, diabetes, schizophrenia and mental illness. Therefore, we need to rethink the drug discovery and therapeutic strategies. In this review, the strategies of selection of cellular signal transduction networks and their dynamics as the targets for drug discovery and pharmacological treatments will be discussed. The properties and analytical methods of these signal transduction networks, internet sources and software tools for performing these strategies will be described. Strategies and procedures of using network- based drug discovery will be emphasized, including multi-targets drug design and network-based drug discovery.