2-Aminopyrimidine Derivatives as New Selective Fibroblast Growth Factor Receptor 4 (FGFR4) Inhibitors.
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ABSTRACT:
SUBMITTER: Mo C
PROVIDER: S-EPMC5430393 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
2-Aminopyrimidine Derivatives as New Selective Fibroblast Growth Factor Receptor 4 (FGFR4) Inhibitors.
Mo Cheng C Zhang Zhang Z Guise Christopher P CP Li Xueqiang X Luo Jinfeng J Tu Zhengchao Z Xu Yong Y Patterson Adam V AV Smaill Jeff B JB Ren Xiaomei X Lu Xiaoyun X Ding Ke K
ACS medicinal chemistry letters 20170331 5
A series of 2-aminopyrimidine derivatives were designed and synthesized as highly selective FGFR4 inhibitors. One of the most promising compounds <b>2n</b> tightly bound FGFR4 with a <i>K</i><sub>d</sub> value of 3.3 nM and potently inhibited its enzymatic activity with an IC<sub>50</sub> value of 2.6 nM, but completely spared FGFR1/2/3. The compound selectively suppressed proliferation of breast cancer cells harboring dysregulated FGFR4 signaling with an IC<sub>50</sub> value of 0.38 μM. Furthe ...[more]
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