Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models

Int J Cancer. 2019 Sep 1;145(5):1346-1357. doi: 10.1002/ijc.32224. Epub 2019 Mar 13.


Aberrant activation in fibroblast growth factor signaling has been implicated in the development of various cancers, including squamous cell lung cancer, squamous cell head and neck carcinoma, colorectal and bladder cancer. Thus, fibroblast growth factor receptors (FGFRs) present promising targets for novel cancer therapeutics. Here, we evaluated the activity of a novel pan-FGFR inhibitor, rogaratinib, in biochemical, cellular and in vivo efficacy studies in a variety of preclinical cancer models. In vitro kinase activity assays demonstrate that rogaratinib potently and selectively inhibits the activity of FGFRs 1, 2, 3 and 4. In line with this, rogaratinib reduced proliferation in FGFR-addicted cancer cell lines of various cancer types including lung, breast, colon and bladder cancer. FGFR and ERK phosphorylation interruption by rogaratinib treatment in several FGFR-amplified cell lines suggests that the anti-proliferative effects are mediated by FGFR/ERK pathway inhibition. Furthermore, rogaratinib exhibited strong in vivo efficacy in several cell line- and patient-derived xenograft models characterized by FGFR overexpression. The observed efficacy of rogaratinib strongly correlated with FGFR mRNA expression levels. These promising results warrant further development of rogaratinib and clinical trials are currently ongoing ( Identifiers: NCT01976741, NCT03410693, NCT03473756).

Keywords: cancer; colorectal cancer; fibroblast growth factor receptor; preclinical models; rogaratinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Drug Screening Assays, Antitumor
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Phosphorylation / drug effects
  • Piperazines / pharmacology*
  • Pyrroles / pharmacology*
  • Random Allocation
  • Rats
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors*
  • Thiophenes / pharmacology*
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Piperazines
  • Pyrroles
  • Receptors, Fibroblast Growth Factor
  • Thiophenes
  • Rogaratinib

Associated data