AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family

  • PR G
  • Mooney L
  • Kilgour E
 et al. 
  • 1


    Mendeley users who have this article in their library.
  • N/A


    Citations of this article.


The fibroblast growth factor (FGF) signaling axis is increasingly implicated in tumorigenesis and chemoresistance. Several small-molecule FGF receptor (FGFR) kinase inhibitors are currently in clinical development; however, the predominant activity of the most advanced of these agents is against the kinase insert domain receptor (KDR), which compromises the FGFR selectivity. Here, we report the pharmacologic profile of AZD4547, a novel and selective inhibitor of the FGFR1, 2, and 3 tyrosine kinases. AZD4547 inhibited recombinant FGFR kinase activity in vitro and suppressed FGFR signaling and growth in tumor cell lines with deregulated FGFR expression. In a representative FGFR-driven human tumor xenograft model, oral administration of AZD4547 was well tolerated and resulted in potent dose-dependent antitumor activity, consistent with plasma exposure and pharmacodynamic modulation of tumor FGFR. Importantly, at efficacious doses, no evidence of anti-KDR-related effects were observed, confirming the in vivo FGFR selectivity of AZD4547. Taken together, our findings show that AZD4547 is a novel selective small-molecule inhibitor of FGFR with potent antitumor activity against FGFR-deregulated tumors in preclinical models. AZD4547 is under clinical investigation for the treatment of FGFR-dependent tumors.

Author-supplied keywords

  • Animals. Antineoplastic Agents
  • ai [Antagonists & Inhibitors]
  • dt [Drug Therapy]. Piperazines
  • pd [Pharmacology]. *Receptors, Fibroblast Growth
  • pd [Pharmacology]. Benzamides
  • pd [Pharmacology]. Cell Line, Tumor. Humans. Mi
  • pd [Pharmacology]. Protein Kinase Inhibitors
  • pd [Pharmacology]. Pyrazoles
  • pk [Pharmacokinetics]. *Antineoplastic Agents
  • pk [Pharmacokinetics]. *Benzamides
  • pk [Pharmacokinetics]. *Piperazines
  • pk [Pharmacokinetics]. *Pyrazoles
  • pk [Pharmacokinetics]. Protein Kinase Inhibitors

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

There are no full text links


  • Gavine PR

  • L Mooney

  • E Kilgour

  • Thomas AP

  • K Al-Kadhimi

  • S Beck

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free