Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase.
Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase.
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DOI：
10.2217/fon.14.51
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Brown JR
中科院分区：
文献类型：
--
作者：
Davids MS;Brown JR
Ibrutinib（原PCI-32765）是一种有效的共价布鲁顿酪氨酸激酶抑制剂，布鲁顿酪氨酸激酶是b细胞受体下游的一种激酶，对b细胞的存活和增殖至关重要。在临床前研究中，依鲁替尼以高亲和力结合布鲁顿酪氨酸激酶，抑制b细胞受体信号传导，降低b细胞活化，诱导凋亡。在临床研究中，ibrutinib具有良好的耐受性，并且在多种血液系统恶性肿瘤中显示出深刻的抗肿瘤活性，最显著的是慢性淋巴细胞白血病（CLL）和套细胞淋巴瘤（MCL），导致美国FDA批准复发性CLL和MCL。正在进行的研究正在评估伊鲁替尼在其他类型的非霍奇金淋巴瘤（如弥漫性大b细胞淋巴瘤和Waldenström的巨球蛋白血症）、CLL和MCL的大型III期研究以及与单克隆抗体和化疗的联合研究中的治疗效果。未来的研究将结合伊鲁替尼与其他有前途的新药物目前正在开发血液恶性肿瘤。
Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton’s tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton’s tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin’s lymphoma, such as diffuse large B-cell lymphoma and Waldenström’s macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies.