ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2023
Infigratinib, a selective FGFR1-3 tyrosine kinase inhibitor, alters dentoalveolar development at high doses.
Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 2 citations in OpenAlex.
- FGFR1 signaling in rheumatoid arthritis: Mechanisms of bone destruction and therapeutic targeting (Review).International journal of molecular medicine · 2026Review
- Inhibition of FGFR signaling with infigratinib improves linear bone growth in the femaleJBMR plus · 2026Article
- Protein-Ligand Interactions in Cardiometabolic Drug Targets: Focus on Weight Loss and Cardioprotection.Molecules (Basel, Switzerland) · 2025Review
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10 authors at 3 institutions in 1 country.
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Abstract
backgroundFibroblast growth factor receptor-3 (FGFR3) gain-of-function mutations are linked to achondroplasia. Infigratinib, a FGFR1-3 tyrosine kinase inhibitor, improves skeletal growth in an achondroplasia mouse model. FGFs and their receptors have critical roles in developing teeth, yet effects of infigratinib on tooth development have not been assessed. Dentoalveolar and craniofacial phenotype of Wistar rats dosed with low (0.1 mg/kg) and high (1.0 mg/kg) dose infigratinib were evaluated using micro-computed tomography, histology, and immunohistochemistry.
resultsMandibular third molars were reduced in size and exhibited aberrant crown and root morphology in 100% of female rats and 80% of male rats at high doses. FGFR3 and FGF18 immunolocalization and extracellular matrix protein expression were unaffected, but cathepsin K (CTSK) was altered by infigratinib. Cranial vault bones exhibited alterations in dimension, volume, and density that were more pronounced in females. In both sexes, interfrontal sutures were significantly more patent with high dose vs vehicle.
conclusionsHigh dose infigratinib administered to rats during early stages affects dental and craniofacial development. Changes in CTSK from infigratinib in female rats suggest FGFR roles in bone homeostasis. While dental and craniofacial disruptions are not expected at therapeutic doses, our findings confirm the importance of dental monitoring in clinical studies.
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