【摘要】 p53在DNA修复、细胞周期阻滞、细胞凋亡、衰老、自噬及代谢等的调控中发挥着重要作用。MDM2和MDM4是p53的关键负调控因子,其抑制剂已成为抗肿瘤药物研究的热点。目前,7个MDM2抑制剂(RG7112,MI-77301,RG7388,AMG232,CGM097,MK-8242及DS-3032b)和1个MDM2/MDM4双重抑制剂(ALRN-6924)已进入临床研究阶段。本文重点从分子发现过程、药理活性、临床研究进展等方面对已进入临床研究的MDM2抑制剂进行综述,此外,还重点介绍MDM2/MDM4双重抑制剂的研究进展。更多还原

【Abstract】 The protein p53 plays an important role in the regulation of DNA repair,cell cycle arrest,apoptosis,senescence,autophagy and metabolism. MDM2 and MDM4 are the key negative regulatory proteins of p53. Inhibition of MDM2 and MDM4 has become a research hotspot in cancer therapy. Currently,seven MDM2 inhibitors( RG7112,MI-77301,RG7388,AMG232,CGM097,MK-8242,DS-3032b) and one MDM2 / MDM4 dual inhibitor( ALRN-6924) have entered clinical trials. This paper highlights small molecule discovery,pharmacological activities and clinical research advances of MDM2 inhibitors in clinical trials. In addition, this review introduces research advances of MDM2 / MDM4 dual inhibitors.更多还原