a Department of Medicinal Chemistry, School of Pharmacy, Health Science Center , Xi'an Jiaotong University , Xi'an , Shaanxi P.R. China.
b Department of Orthopedics , People's Hospital of Fufeng County in Shaanxi Province , Baoji , Shaanxi P.R. China.
Expert Opin Ther Pat. 2019 Apr;29(4):217-241. doi: 10.1080/13543776.2019.1594777.
Bruton's tyrosine kinase (BTK) plays a critical role in the regulation of survival, proliferation, activation and differentiation of B-lineage cells. It participates by regulating multiple cellular signaling pathways, including B cell receptor and FcR signaling cascades. BTK is abundantly expressed and constitutively active in the pathogenesis of B cell hematological malignancies, as well as several autoimmune diseases. Therefore, BTK is considered as an attractive target for treatment of B-lineage lymphomas, leukemias, and some autoimmune diseases. Many industry and academia efforts have been made to explore small molecular BTK inhibitors.
This review aims to provide an overview of the patented BTK inhibitors for the treatment of cancer from 2010 to 2018.
BTK inhibitors attract much interest for their therapeutic potential in the treatment of cancers and autoimmune diseases, especially for B cell hematological malignancies. In 2013, ibrutinib was approved by the FDA as the first-in-class BTK inhibitors for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), and now it is also undergoing clinical evaluation for other indications in either single or combined therapy. It is clear that BTK inhibitors can provide a promising clinical benefit in treating B-lineage lymphomas and leukemias.
布鲁顿酪氨酸激酶（BTK）在 B 细胞谱系细胞的存活、增殖、激活和分化的调控中发挥着关键作用。它通过调节多种细胞信号通路，包括 B 细胞受体和 FcR 信号级联来参与其中。BTK 在 B 细胞血液恶性肿瘤以及多种自身免疫性疾病的发病机制中大量表达且持续激活。因此，BTK 被认为是治疗 B 细胞淋巴瘤、白血病和某些自身免疫性疾病的有吸引力的靶点。许多工业界和学术界都在努力探索小分子 BTK 抑制剂。
本综述旨在概述 2010 年至 2018 年期间用于治疗癌症的专利 BTK 抑制剂。
BTK 抑制剂因其在癌症和自身免疫性疾病治疗方面的治疗潜力而备受关注，尤其是在 B 细胞血液恶性肿瘤方面。2013 年，依鲁替尼被 FDA 批准为首个用于治疗套细胞淋巴瘤（MCL）和慢性淋巴细胞白血病（CLL）的 BTK 抑制剂，目前它也正在进行单药或联合治疗的其他适应症的临床试验评估。很明显，BTK 抑制剂在治疗 B 细胞淋巴瘤和白血病方面可以提供有前景的临床获益。
