Background:

AZD4547 is a potent, specific, orally bioavailable fibroblast growth factors receptor (FGFR) tyrosine kinase inhibitor. It inhibits FGFR1, FGFR2, and FGFR3 with IC50 values of 12, 2 and 40 nM, respectively. AZD4547 has also been reported to block FGFR1, FGFR2, and FGFR3 autophosphorylation with IC50 values of 0.2, 2.5, and 1.8 nM, respectively [1].

AZD4547 has been demonstrated to inhibit cell proliferation and inhibit FGFRs and their downstream markers including PLCg and FRS2 phosphorylation in breast cell line Sum52-PE (expressing wild-type FGFR2), multiple myeloma line KMS11 (expressing Y373C mutated FGFR3 protein) and acute myeloid leukemia cell line KG1a (expressing wild-type FGFR1) [1].

Anti-carcinoma effect of AZD4547 has been observed in lung cancer xeonograft mice orally treated with AZD4547. This effect is believed to be via the specifically inhibition of the activity of FGFR but not kinase insert domain receptor (KDR)[1].

参考文献:
[1] Gavine PR1,?Mooney L,?Kilgour E,?Thomas AP,?Al-Kadhimi K,?Beck S,?Rooney C,?Coleman T,?Baker D,?Mellor MJ,?Brooks AN,?Klinowska T. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res.?2012 Apr 15;72(8):2045-56.