抗凋亡蛋白Mcl-1小分子抑制剂研究进展

Progress on Mcl-1 small molecule inhibitors

Bcl-2蛋白家族在内源性凋亡中起到关键的调控作用.髓细胞白血病因子-1(Mcl-1)作为Bcl-2家族的抗凋亡蛋白成员之一,在多种肿瘤细胞中高表达.Mcl-1蛋白的高表达不仅促进肿瘤的产生和发展,还会导致肿瘤细胞对化疗药物产生耐药性,因此靶向于Mcl-1的小分子抑制剂是十分具有前景的抗肿瘤药物.本文对近年来国内外在Mcl-1抑制剂方面的研究进行了综述,通过对天然产物以及化学合成小分子构效关系的分析与总结,对Mcl-1抑制剂的发展进行了总结与展望.

The Bcl-2 family of proteins serve as vital regulators in the intrinsic cell death pathway. Myeloid cell leukemia 1 （Mcl-1）, a prosurvival member of the Bcl-2 family of proteins, is over-expressed in many tumor types. The over-expressed Mcl-1 protein promotes the formation and development of tumor and causes the resistance to several chemotherapeutic agents and B cl-2/Bcl-XL inhibitors such as ABT-737 and ABT-199. Mcl-1 appears to be a promising cancer target as important as other Bcl-2 anti-apoptotic proteins. Encouragingly, last half-decade has witnessed a rapid surge of interest towards the discovery of Mcl-1 inhibitors. This review highlighted the recent progress of Mcl-1 inhibitors.