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Updated: Dec 29, 2025
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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma
Yen Vo-Hoang1, Sergio Paiva1, Leilei He2
1Institut des Biomolécules Max Mousseron, UMR 5247, CNRS-UM-ENSCM, UFR des Sciences Pharmaceutiques et Biologiques, 15 avenue Charles Flahault, 34093 Montpellier Cedex 5, France.
Background:
Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related deaths and calls for new druggable targets. We have previously highlighted the critical role of ADP-ribosylation factor-1 (Arf1) activation in HNSCC. In the present study, we address the question whether targeting Arf1 could be proposed as a valuable strategy against HNSCC.
Methods:
We rationally designed and synthesized constrained ATC-based (4-amino-(methyl)-1,3-thiazole-5-carboxylic acid) γ-dipeptides to block Arf1 activation. We evaluated the effects of these γ-dipeptides in HNSCC cells: The cell viability was determined in 2D and 3D cell cultures after 72 h treatment and Arf1 protein levels and activity were assessed by GGA3 pull-down and Western blotting assays.
Results:
Targeting Arf1 offers a valuable strategy to counter HNSCC. Our new Arf1-targeting compounds revealed a strong in vitro cytotoxicity against HNSCC cells, through inhibiting Arf1 activation and its downstream pathways.
Conclusions:
Arf1-targeting γ-dipeptides developed in this study may represent a promising targeted therapeutic to improve managing the HNSCC disease.
Insights
New ADP-ribosylation factor-1 (Arf1) targeting compounds show promise for head and neck squamous cell carcinoma (HNSCC). These Arf1-targeting γ-dipeptides demonstrate significant in vitro cytotoxicity against HNSCC cells, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a significant cause of cancer mortality.
- Identifying novel druggable targets is crucial for advancing HNSCC treatment.
- Previous research identified ADP-ribosylation factor-1 (Arf1) activation as critical in HNSCC.
Purpose of the Study:
- To investigate the potential of targeting Arf1 as a therapeutic strategy for HNSCC.
- To design and synthesize novel Arf1 inhibitors.
- To evaluate the efficacy of these inhibitors in HNSCC models.
Main Methods:
- Rational design and synthesis of constrained ATC-based (4-amino-(methyl)-1,3-thiazole-5-carboxylic acid) γ-dipeptides.
- Evaluation of γ-dipeptide effects on HNSCC cell viability in 2D and 3D cultures.
- Assessment of Arf1 protein levels and activity using GGA3 pull-down and Western blotting.
Main Results:
- The synthesized γ-dipeptides effectively target Arf1.
- These compounds exhibited strong in vitro cytotoxicity against HNSCC cells.
- Inhibition of Arf1 activation and its downstream pathways was confirmed.
Conclusions:
- Targeting Arf1 presents a viable strategy for combating HNSCC.
- The developed Arf1-targeting γ-dipeptides show promising therapeutic potential.
- These compounds could lead to improved management of HNSCC disease.
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