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Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
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An overview of the binding models of FGFR tyrosine kinases in complex with small molecule inhibitors

Weiyan Cheng1, Mixiang Wang2, Xin Tian1

  • 1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

European Journal of Medicinal Chemistry
|December 4, 2016
PubMed

Insights

Fibroblast growth factor receptor (FGFR) signaling drives solid tumor progression. This review examines FGFR co-crystal structures with inhibitors, detailing binding models and pharmacological activities for anticancer therapy development.

Area of Science:

  • Oncology
  • Pharmacology
  • Structural Biology

Background:

  • The fibroblast growth factor receptor (FGFR) family, comprising FGFR1-4, are receptor tyrosine kinases (RTKs).
  • Aberrant FGFR signaling is implicated in the progression of various solid tumors.
  • Targeting FGFRs presents a promising strategy for anticancer drug development.

Purpose of the Study:

  • To review reported co-crystal structures of FGFRs in complex with inhibitors.
  • To analyze the binding models of these FGFR/inhibitor complexes.
  • To discuss the pharmacological activities of the inhibitors targeting FGFRs.

Main Methods:

  • Literature review of published co-crystal structures.
  • Analysis of structural data for FGFR/inhibitor interactions.
  • Compilation and summary of pharmacological data for identified inhibitors.

Main Results:

  • Detailed examination of co-crystal structures reveals specific binding modes of various inhibitors to FGFRs.
  • Understanding these binding models aids in elucidating mechanisms of action.
  • Pharmacological data highlights the efficacy and potential of these inhibitors in preclinical settings.

Conclusions:

  • Co-crystal structures provide critical insights into FGFR inhibitor mechanisms.
  • Structural information facilitates the design and optimization of novel FGFR-targeted anticancer agents.
  • Targeting FGFR signaling remains a key focus in solid tumor therapeutic strategies.
Keywords:
Crystal structureDFG-in/outFGFRIrreversiblePharmacological activitySmall molecule inhibitor

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