布鲁顿酪氨酸激酶靶向药物的研究进展

Progress on Bruton's Tyrosine Kinase Targeted Drugs

关键词:  布鲁顿酪氨酸激酶  B细胞抗原受体  靶向药物  B细胞恶性肿瘤  自身免疫病  靶向蛋白降解嵌合体

Key words:  Bruton's tyrosine kinase  B cell antigen receptor  targeted drugs  B cell malignancies  autoimmune disease  proteolysis-targeting chimeras

摘要:

布鲁顿酪氨酸激酶（Bruton's tyrosine kinase，BTK）是B细胞抗原受体信号转导通路中的关键激酶，参与B细胞增殖、分化和凋亡的调节，同时在多种信号通路的调控及肿瘤和炎症的发生和发展中也起着重要作用，已成为治疗恶性血液病和自身免疫性疾病的重要靶点。目前已上市的BTK靶向药物依鲁替尼、阿卡替尼和泽布替尼，对B细胞恶性肿瘤显示出较好的临床疗效，此外已有多个药物进入临床研究，表现出较好的开发前景。靶向BTK的靶向蛋白降解嵌合体分子的发展，有望解决依鲁替尼引起的耐药，更好地推动BTK靶向药物的研发。本文主要对BTK靶向药物的研究进展进行综述，为合理开发BTK靶向药物提供启示。

Abstract:

Bruton's tyrosine kinase(BTK) is a key kinase in the B cell antigen receptor signaling pathway, involved in B cell proliferation, differentiation and apoptosis, also associated with multiple signaling pathways and the occurrence and development of inflammation and tumors, has become an important target for the treatment of hematological malignancies and autoimmune diseases. The currently marketed BTK targeting drugs Ibrutinib, Acalabrutinib and Zanubrutinib have shown satisfactory clinical efficacy for B-cell malignancies. In addition, a number of drugs have entered clinical research and performed well. The proteolysis-targeting chimeras targeting BTK is a promising strategy to solve the resistance of Ibrutinib and promoting the development of BTK targeted drugs. This paper reviews the progress of BTK targeted drugs, and provides inspiration for further research of BTK targeted drugs.