Novartis Pharma AG, Basel, Switzerland.
Mol Cancer Ther. 2011 Sep;10(9):1542-52. doi: 10.1158/1535-7163.MCT-11-0426. Epub 2011 Jul 15.
We describe here the identification and characterization of 2 novel inhibitors of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases. The compounds exhibit selective inhibition of FGFR over the closely related VEGFR2 receptor in cell lines and in vivo. The pharmacologic profile of these inhibitors was defined using a panel of human tumor cell lines characterized for specific mutations, amplifications, or translocations known to activate one of the four FGFR receptor isoforms. This pharmacology defines a profile for inhibitors that are likely to be of use in clinical settings in disease types where FGFR is shown to play an important role.
我们在这里描述了两种新型成纤维细胞生长因子受体（FGFR）家族受体酪氨酸激酶抑制剂的鉴定和特性。这些化合物在细胞系和体内表现出对 FGFR 的选择性抑制，而对密切相关的 VEGFR2 受体没有抑制作用。这些抑制剂的药理特性是使用一组具有特定突变、扩增或易位的人类肿瘤细胞系来定义的，这些突变、扩增或易位已知可激活四种 FGFR 受体亚型之一。这种药理学为抑制剂的应用提供了一个概况，这些抑制剂可能在 FGFR 发挥重要作用的疾病类型的临床环境中有用。
