Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth
Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth
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DOI：
10.1158/1535-7163.mct-15-0923
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发表时间：
2016-12-01
影响因子：
5.7
通讯作者：
Elias, Laurence
中科院分区：
文献类型：
--
作者：
Chen, Jun;Kinoshita, Taisei;Elias, Laurence
伊布鲁替尼是一种有效的小分子布鲁顿酪氨酸激酶(BTK)抑制剂，用于治疗B细胞恶性肿瘤。在BTK的ATP结合区，ibrutinib与Cys481共价结合。这个半胱氨酸残基在其他9种酪氨酸激酶中是保守的，包括HER2和EGFR，可以作为靶点。对大量细胞株的筛选表明，伊布鲁替尼对一些实体瘤细胞有生长抑制作用，包括其他HER2/EGFR抑制剂抑制的实体瘤细胞。在敏感细胞系中，HER2过表达的乳腺癌细胞系对伊布鲁替尼的抑制作用最强(
Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (