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Discovery of Rogaratinib (BAY 1163877): a pan-FGFR Inhibitor

Marie-Pierre Collin1, Mario Lobell1, Walter Hübsch1

  • 1Department of Medicinal Chemistry, Drug Discovery, Bayer AG, Postfach 101709, 42096, Wuppertal, Germany.

Chemmedchem
|February 17, 2018
PubMed

Insights

Rogaratinib is a new oral cancer drug targeting all fibroblast growth factor receptors (FGFR1-4). Its discovery through structure-based design and optimization is detailed, along with its pharmacokinetic profile.

Area of Science:

  • Oncology
  • Medicinal Chemistry
  • Pharmacology

Background:

  • Fibroblast growth factor receptors (FGFRs) are implicated in various cancers.
  • Targeting FGFRs offers a therapeutic strategy for cancer treatment.
  • Development of potent and selective FGFR inhibitors is ongoing.

Purpose of the Study:

  • To report the discovery of Rogaratinib (BAY 1163877), a novel pan-fibroblast growth factor receptor (FGFR) inhibitor.
  • To describe the de novo structure-based design and medicinal chemistry optimization process.
  • To present the pharmacokinetic profile of Rogaratinib.

Main Methods:

  • Structure-based drug design utilizing computational modeling.
  • Medicinal chemistry optimization to enhance potency and selectivity.
  • In vitro and in vivo assays to evaluate pharmacological activity.
  • Pharmacokinetic studies to assess drug absorption, distribution, metabolism, and excretion.

Main Results:

  • Rogaratinib (BAY 1163877) was identified as a highly potent and selective inhibitor of FGFR1-4.
  • The drug was successfully developed through de novo structure-based design and optimization.
  • Favorable pharmacokinetic properties supporting oral administration were observed.

Conclusions:

  • Rogaratinib is a promising orally available pan-FGFR inhibitor.
  • Its discovery highlights the success of structure-based design in developing targeted cancer therapies.
  • Rogaratinib is currently undergoing Phase 1 clinical trials for cancer treatment.
Keywords:
cancerfibroblast growth factor receptor (FGFR)inhibitorsmedicinal chemistrystructure-based design

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