靶向作用p53药物的研究进展

Research progress on drugs targeting p53

随着对肿瘤发生、发展的认识,抗肿瘤药物的靶向研究进入了一个新的阶段。p53基因是重要的抑癌基因,其编码的p53蛋白在细胞周期调控、DNA修复和诱导凋亡等方面起着关键的作用,p53基因的突变是肿瘤发生的重要因素之一。因此,p53可能成为抗肿瘤药的一个重要的靶点基因。随着很多小分子药物筛选方法不断的发现和运用,目前已有部分以p53为靶点的化合物研究报道,并且以突变p53为靶点的化合物APR-246已进入临床II期试验。同时,以p53为靶点的化合物研究推动着蛋白相互作用和蛋白突变体构象领域药物的发现。该文主要讨论以p53为靶点的药物的研究前沿,并分类阐述该类药物作用特点和机制。

With the understanding of the development and pro-gress of the cancer,the research of targeted cancer drug devel-opment reaches into a new era.p53 is an important tumor sup-pressor gene,the protein coded by p53 plays a critical role in tumor suppression mainly by inducing cell cycle regulation, DNA repair and apoptosis.Nowadays,p53 becomes a relatively attractive target for anti-cancer drug development and there are some drugs targeting p53,moreover,APR-246 which targets mutant p53 is in Phase Ⅱ clinical trial.In addition,it facilitates＆amp;nbsp;drugs discovery programmes in the challenging area of protein-protein interactions and mutant protein conformational change. The review discusses the research progress of drugs which target p53 and elucidates the characteristics and mechanisms of these compounds.