急性髓细胞性白血病（AML）是成年人血液系统常见的恶性癌症。临床治疗以化疗和造血干细胞移植为主，鉴于现有的治疗方法的局限性及不适用这两种治疗方法病人的低治愈率，迫切需求新的治疗方案。在研究BTK激酶抑制剂依鲁替尼的过程中，我们发现了依鲁替尼的衍生物MM2-48，它在激酶组中的选择性与依鲁替尼几乎相同，能够强烈的抑制BTK激酶。但是不同的是，它对AML细胞的生长具有很强的抑制作用。结合基因沉默技术进一步研究发现，MM2-48对AML细胞的抗增殖活性并不依赖于靶点蛋白BTK激酶，而是通过其它的未知靶点起作用。因此我们拟运用质谱蛋白质组学及基因表达图谱分析等技术探寻MM2-48在AML中起作用新靶点，在蛋白水平、细胞水平、动物模型水平验证靶点的有效性，并采用分子生物学、细胞生物、化学生物学的方法初步阐明其在AML的作用机制，为发现新的药物开发靶点、探究AML的发病机制以及治疗提供新的思路。

Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, which is characterized by the rapid growth of abnormal white blood cells that build up in the bone marrow and interfere with the production of normal blood cells. Clinical treatment of AML remains poor yet, especially for patients over 60 years who comprises of the majority of this disease. Cure rates in these patients, who typically do not tolerate high-dose chemotherapy and stem cell transplantation, are below 20% and have not been improved significantly in the past 2 decades. Hence, new therapies are urgently needed. Recently, during the studying the BTK kinase inhibitor ibrutinib, We found a derivative of ibrutinb, MM2-48, which is also a potent BTK kinase inhibitor, exhibited strong anti-proliferation effect against acute myeloid leukemia cells. However, knocking down of BTK kinase in HEL and NB4 cells did not affect the anti-proliferative effect of MM2-48, which indicated that MM2-48 might exert its inhibitory activity through other targets but not BTK kinase in the AML cells. Hence, we propose to use activity-based protein profiling and gene expression profiling technology to identify the new target of MM2-48. In addition, through biochemistry, cell biology, molecular biology methods to validate and study the mechanism of MM2-48’s effect in vitro and in vivo in the AML. We hope that this study will provide a pave the way for finding a new drug discovery targets and better understanding of pathology of AML.