Mechanism of action: Fibroblast growth factor receptor (FGFR) tyrosine kinase family inhibitor

Preclinical pharmacology

AZD4547 is a potent inhibitor of FGFR-1,2 and 3 (IC50 < 5nM) with weaker activity against FGFR-4 (IC50 165nM), KDR (24nM) , MARKs (60nM), and IGF1R (581nM) of 73 other kinases  screened.  In cell-lines, overexpressing the relevant receptor, AZD4547 potently inhibits the kinase activity of FGFR 1-3 (IC50 <50nM), while again be weaker for KDR (IC50 258nM) and IGF1R (IC50 829 ± 40nM). AZD4547 was shown to inhibit proliferation, in a dose-dependent manner, in several cancer cell-lines, known to overexpress fibroblast growth factor (FGF) receptors. In KMS11, KG1a and SUM52PE cell-lines, AZD4547 inhibited FGFR tyrosyl phosphorylation and the phosphorylation of the downstream signalling molecules p42/p44MAP kinases.

Oral treatment of mice bearing KMS11 (myeloma) xenografts, either once or twice daily with AZD4547 resulted in dose-dependent tumour growth inhibition. AZD4547 similarly induced inhibition of tumour growth in mice bearing KG1a (leukemic) xenografts.

Additional Information

Clinical Trials for this compound

See all of the Clinical Trials currently associated with this compound:

Publications for this compound

Find out more about this compound by reading related Publications:

Cancer Research

AZD4547: An Orally Bioavailable, Potent, and Selective Inhibitor of the Fibroblast Growth Factor Receptor Tyrosine Kinase Family

Gene information from the NCBi

This compound works on the following genes: