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Updated: Sep 18, 2025

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
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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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Structure-based identification of potent fibroblast growth factor receptor 4 (FGFR4) inhibitors as potential

Lin Fan1, Hui Xie1, Weiyu Wang1

  • 1Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, China.

Peerj
|June 23, 2025
PubMed

Insights

Researchers identified two potential FGFR4 inhibitors, MFCD00832235 and MFCD00204244, using virtual screening. These compounds show promise for developing new cancer treatments, particularly for hepatocellular carcinoma.

Area of Science:

  • Medicinal Chemistry
  • Computational Drug Discovery
  • Oncology

Background:

  • Fibroblast growth factor receptor 4 (FGFR4) is implicated in various cancers, presenting a target for therapeutic intervention.
  • Dysregulated FGFR4 signaling contributes to tumor progression in cancers like hepatocellular carcinoma.

Purpose of the Study:

  • To identify novel small molecule inhibitors of FGFR4 through structure-based virtual screening.
  • To evaluate the drug-likeness and binding stability of identified candidates.
  • To assess the in vitro efficacy of lead compounds against cancer cells.

Main Methods:

  • Structure-based virtual screening of chemical libraries against FGFR4.
  • Filtering of compounds using PAINS and ADME/T property assessments.
  • Quantum mechanical (QM) and molecular dynamics (MD) simulations to predict stability and binding.
  • In vitro cell-based assays to determine inhibitory concentrations (IC50).

Main Results:

  • Two promising FGFR4 inhibitors, MFCD00832235 and MFCD00204244, were identified.
  • QM calculations indicated high dynamic stability (large HOMO-LUMO gap) for both compounds.
  • MD simulations and MM/PBSA calculations confirmed stable binding to the FGFR4 ATP-binding site.
  • Both compounds demonstrated inhibitory activity against HepG2 cells (liver cancer cell line).

Conclusions:

  • MFCD00832235 and MFCD00204244 are validated as potential FGFR4 inhibitors.
  • These compounds represent promising starting points for the development of novel FGFR4-targeted cancer therapeutics.
  • Further optimization may lead to effective treatments for hepatocellular carcinoma and other FGFR4-driven cancers.
Keywords:
ADMET predictionFibroblast growth factor receptor 4 (FGFR4)Hepatocellular carcinomaMD simulationQM calculationsVirtual screening

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