Bcl-2和Mcl-1是保护AML细胞不发生凋亡的重要抗凋亡蛋白，同时抑制Bcl-2和Mcl-1可能对不良预后型AML更为有效。在对Bcl-2家族蛋白空间结构的认识以及分子模拟的基础上，对兼有抑制Mcl-1和Bcl-2活性的吲哚类化合物A9和苯并咪唑类化合物B3进行结构优化和构效关系研究，寻找双重抑制Mcl-1和Bcl-2，但不抑制Bcl-xL的化合物。有望发现一类新型低毒的Bcl-2/Mcl-1双重抑制剂用于治疗AML。

We aim to develop dual Bcl-2/Mcl-1 inhibitors for acute myeloid leukemia (AML) treatment. Bcl-2 and Mcl-1 are two main antiapoptotic proteins to protect cell from apoptosis in AML and inhibition of both proteins are required for apoptosis induction. Based on the structural analysis of the Bcl-2, Bcl-xL and Mcl-1 and virtual screening with the in-house library, we found that the lead compounds A9 and B3 bearing indol and benzimidazole, respectively, have dual inhibitory effects on Mcl-1 and Bcl-2. Both compounds will be further optimized to increase their inhibitory ability on Mcl-1/Bcl-2 while sparing Bcl-xL. We will develop a novel group of Bcl-2/Mcl-1 inhibitors for AML treatment without severe toxicity.