B淋巴瘤是血液系统最常见的恶性肿瘤，其致死率居高不下。靶向SYK的小分子药物为B淋巴瘤的治疗带来了希望，但临床治疗中肿瘤已对常用的小分子靶向药物产生抵抗而导致治疗失败。因此，开发针对B淋巴瘤的新型高效特异的靶向小分子药物是目前亟待解决的问题。我们前期经设计、合成及体外筛选得到的新型靶向SYK的小分子抑制剂SKLB-850能有效抑制肿瘤细胞生长，诱导肿瘤细胞的凋亡和干扰HUVEC细胞的侵袭和转移。在此研究基础上，本课题拟进一步探讨SKLB-850对B淋巴瘤的侵袭、转移及肿瘤干细胞的作用，并结合临床标本进行多层次的分析评价。同时利用结构生物学、蛋白质组学、生物信息学等方法深入研究SKLB-850调控SYK信号通路的抗肿瘤分子机制，并检测SKLB-850与氟达拉滨联合应用治疗B淋巴瘤的协同增效作用。本研究为将来B淋巴瘤的靶向治疗提供了实验基础和新的思路。

B cell lymphoma is considered as one of the most aggressive and deadliest cancers and current targeted therapies of B cell lymphoma often suffer limited efficacy or drug resistance. Discovery of novel target inhibitors as anti-B cell lymphoma drug candidates is still needed. Previous studies showed that SYK was a target for the treatment of B cell lymphoma. However, the activity of these agents is relatively poor. Thus, there is still necessity to discover more potent agents, in particular with novel chemical molecular. SKLB-850, a novel small-molecule compound discovered by us recently, showed potent anti-tumor activity in human B cell lymphoma model and inhibition effect of metastasis and invasion in HUVECs, inducing tumor cell apoptosis. We will use structural biology analysis, differential proteomics approaches and bioinformatics methods for investigating the mechanisms of anti-tumor effects of SKLB-850 and associated signaling pathways. Then, we will explore the antitumor effect of combined with a drug fludarabine. This research could yield new insights into B cell lymphoma targeted therapy in the future.