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Updated: Jul 6, 2026
Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
Published on: September 30, 2019
Identification of small molecule inhibitors targeting FGFR through molecular docking-based screening
Weibo Hou1, Kun Liu2, Ping Wang1
1College of Bioinformatics Science and Technology, National Health Commission Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, Heilongjiang, China.
Background:
FGFRs genetic alterations such as mutations, amplifications, and chromosomal translocations are prevalent in cancers, leading to the initiation and progression of tumors by enhancing FGFR signaling. The substantial problems arising from the lack of decisive clinical evidence have resulted in the cessation of some inhibitor applications, and identifying effective small molecule inhibitors that selectively target FGFRs can advance the therapy of cancers driven by FGFRs abnormalities.
Methods:
The three-dimensional structure of the FGFR1/2/3/4 protein and the amino acid positions within the tyrosine kinase domain were downloaded from the PDB database, and small molecule data were extracted from the ZINC15 database. Then, we used molecular docking and dynamics simulations to assess compounds interacting with FGFR proteins, and screening potential small molecules targeting FGFR. Finally, we evaluated its effects by two CRC cell line HCT116 and NCI-H716.
Results:
In the study, by docking with 2.8 million small molecules, we identified three promising FGFR small molecule inhibitors ranked in the top average absolute difference in free energy. By evaluating the binding stability of the docking pose of the three compounds, we found that ZINC000101867325 could form the stable binding interactions with FGFR1/2/3. And, ZINC000101867325 inhibited the activity of FGFR signaling, and resulted in cell apoptosis and decrease in cell proliferation and migration in colorectal cancer cell lines. In addition, ZINC000101867325 is also predicted to target FGFR2 mutations in colorectal cancer patients.
Conclusion:
We predicted three small molecules targeting FGFRs, and ZINC000101867325 shows superior chemical bond types and stability with FGFR1/2/3, and inhibits FGFR signaling in CRC cell lines. This study provides novel FGFRs inhibitors, which enrich treatment strategies for cancers.
Insights
We identified ZINC000101867325, a novel small molecule inhibitor targeting Fibroblast Growth Factor Receptors (FGFRs). This compound effectively inhibits FGFR signaling, leading to reduced proliferation and increased apoptosis in colorectal cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Fibroblast Growth Factor Receptors (FGFRs) genetic alterations are common in various cancers, driving tumor initiation and progression.
- Dysregulated FGFR signaling presents a therapeutic challenge due to limited clinical evidence for existing inhibitors.
- Developing selective small molecule inhibitors for FGFRs is crucial for advancing cancer therapy.
Purpose of the Study:
- To identify novel small molecule inhibitors targeting FGFRs.
- To evaluate the efficacy of identified inhibitors in colorectal cancer models.
- To provide new therapeutic strategies for cancers driven by FGFR abnormalities.
Main Methods:
- Downloaded FGFR1/2/3/4 protein structures from the PDB database.
- Extracted small molecule data from the ZINC15 database.
- Utilized molecular docking and dynamics simulations to screen potential FGFR inhibitors.
- Assessed the effects of lead compounds on colorectal cancer cell lines (HCT116 and NCI-H716).
Main Results:
- Identified three promising FGFR small molecule inhibitors from docking 2.8 million compounds.
- ZINC000101867325 demonstrated stable binding with FGFR1/2/3 and inhibited FGFR signaling.
- ZINC000101867325 reduced cell proliferation and migration while inducing apoptosis in colorectal cancer cell lines.
- ZINC000101867325 is predicted to target FGFR2 mutations in colorectal cancer patients.
Conclusions:
- ZINC000101867325 is a potent FGFR inhibitor with superior binding stability.
- This novel inhibitor effectively targets FGFR signaling in colorectal cancer cell lines.
- The study offers new FGFR inhibitors to enhance cancer treatment strategies.
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