【作者】 郭彦伸； 毛雪石； 郭宗儒；

【Author】 Yanshen Guo, Xueshi Mao, Zongru Guo* Institute Materia Medica, Chinese Academy of Medical Sciences, 10050, Beijing

【机构】 中国医学科学院药物研究所；

【摘要】 尽管单一靶点的药物在临床上表现出显著的疗效,但是随着人们对系统生物学认识的提高和药理学研究的逐渐深入,发现它们也存在着明显的不良反应,而且大部分单一靶点抗肿瘤药物的有效率仅为10%左右,人们逐渐认识到,单一分子靶点药物之间的联合应用,以及作用于多个分子靶点的“多靶点”药物在治疗功能失调类疾病时将起到重要作用。本文从最近有关多靶点配体药物分子设计的文献中选取了大量的实例,从不同的角度对比分析了单靶点药物的美中不足,以生动的实例介绍了多靶点药物的优势,详细介绍了多靶点配体药物分子设计的方法和需要优化的参数,综述了多靶点药物的研发和应用现状和研究进展。更多还原

【Abstract】 With the advancement of studies on pharmacology and system biology, target-focused drugs which have provided notable success in clinic currently display evident side effect and most one-target anti-cancer drugs have lower effective ratio. Increasingly it is being recognized that the combine administration of selective ligands (one-target drugs) and designed multiple ligands can modulate a balance of several targets and provide a superior therapeutic effect and side effect profile compared with the action of one-target drugs. An particular analysis is performed on the selective ligands and an opinion that one target drugs have defects as well as merits is raised. The predominance of the designed multiple ligands is introduced simultaneously by enumerating some successful examples. The approaches of design multiple ligands and the procedure of optimization are elucidated in detail. The key challenge in the design of multiple ligand is obtaining a balanced activity at each target of interest while simultaneously achieving a wider selectivity and a suitable pharmacokinetic profile. The trends and insight of multiple ligands might help medicinal chemists discover the novel generation drugs.更多还原