Bruton tyrosine kinase (BTK) is a key kinase in the B cell antigen receptor signal transduction pathway, which is involved in the regulation of the proliferation, differentiation and apoptosis of B cells. BTK has become a significant target for the treatment of hematological malignancies and autoimmune diseases. Ibrutinib, the first-generation BTK inhibitor, has made a great contribution to the treatment of B cell malignant tumors, but there are still some problems such as resistance or miss target of site mutation. Therefore, there is an imperative need to develop novel BTK inhibitors to overcome these problems. Besides, proteolysis targeting chimera (PROTAC) technology has been successfully applied to the development of BTK degradation agents, which has opened a fresh way for the BTK targeted treatment. This paper reviews the biological function of BTK, the discovery and development of BTK targeted drugs as a promising cancer therapy. It mainly reviews the binding sites and structural characteristics of BTK, structure–activity relationships, activity and drug resistance of BTK inhibitors, as well as potential treatment strategies to overcome the resistance of BTK, which provides a reference for the rational design and development of new powerful BTK inhibitors.

布鲁顿酪氨酸激酶(BTK)是B细胞抗原受体信号转导通路中的关键激酶，参与调控B细胞增殖、分化和凋亡。BTK已成为治疗血液系统恶性肿瘤和自身免疫性疾病的重要靶点。依鲁替尼第一代BTK抑制剂为B细胞恶性肿瘤的治疗做出了巨大贡献，但仍存在耐药或位点突变漏靶等问题。因此，迫切需要开发新的BTK抑制剂来克服这些问题。此外，蛋白水解靶向嵌合体（PROTAC）技术已成功应用于BTK降解剂的开发，为BTK靶向治疗开辟了一条新途径。本文回顾了 BTK 的生物学功能，以及 BTK 靶向药物作为一种有前途的癌症治疗方法的发现和开发。主要综述了BTK的结合位点和结构特征、构效关系、BTK抑制剂的活性和耐药性、