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Updated: Jun 14, 2026
07:32
Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
Published on: September 30, 2019
A structure-guided approach to creating covalent FGFR inhibitors
Wenjun Zhou1, Wooyoung Hur, Ultan McDermott
1Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Chemistry & Biology
|March 27, 2010
Summary
Researchers developed FIIN-1, a novel irreversible inhibitor targeting fibroblast growth factor receptors (FGFR1-4). This potent compound effectively inhibits FGFR-dependent cancer cells and may lead to new cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Fibroblast growth factor receptors (FGFRs) are implicated in various cancers, making them key therapeutic targets.
- Developing selective inhibitors for FGFR tyrosine kinases is crucial for cancer treatment.
Purpose of the Study:
- To develop and characterize a novel, potent, and selective irreversible inhibitor for FGFR1, 2, 3, and 4.
- To evaluate the efficacy of the inhibitor in FGFR-dependent cancer cell lines.
Main Methods:
- Chemical synthesis of FIIN-1, a covalent inhibitor targeting FGFR.
- In vitro assays to assess inhibition of FGFR1-transformed Ba/F3 cells and cancer cell lines.
- Use of a biotinylated derivative (FIIN-1-biotin) to confirm covalent labeling of FGFR1.
Main Results:
- FIIN-1 demonstrated potent inhibition of Tel-FGFR1-transformed Ba/F3 cells with an EC50 of 14 nM.
- The inhibitor effectively suppressed numerous FGFR-dependent cancer cell lines.
- FIIN-1-biotin confirmed covalent binding to FGFR1 at Cys486.
Conclusions:
- FIIN-1 is the first potent and selective irreversible inhibitor developed for FGFR1-4.
- FIIN-1 serves as a valuable probe for studying FGFR-dependent cellular processes.
- This inhibitor offers a potential starting point for developing therapeutics against wild-type and resistant FGFR kinases.
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