Evidence map›Paper›PMID 37435833›Full record

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.

Zachary D Michel, Sarah F Aitken, Omar D Glover, Lucy O Alejandro, Davide Randazzo, Carl Dambkowski, David Martin, Michael T Collins, Martha J Somerman, Emily Y Chu

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 37% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Zachary D MichelSkeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Sarah F AitkenLaboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland, USA.
Omar D GloverLaboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland, USA.
Lucy O AlejandroLaboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland, USA.
Davide RandazzoLight Imaging Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Carl DambkowskiQED Therapeutics, San Francisco, California, USA.
David MartinQED Therapeutics, San Francisco, California, USA.
Michael T CollinsSkeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Martha J SomermanLaboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland, USA.
Emily Y ChuLaboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-7763-2928
National Institutes of Health · USRapt Therapeutics (United States) · USUniversity of Maryland, Baltimore · US

Funding

NIAMS Light Imaging FacilityZICAR041186 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI RANDAZZO, DAVIDE · 2010 to 2025
$18.2M
Role of modulators of Pi/PPi in cementum formation and regenerationR00DE031148 · NIDCR · UNIVERSITY OF MARYLAND BALTIMORE · PI CHU, EMILY YIN · 2021 to 2023
$747k
NIDCR NIH HHS R00 DE031148NIDCR NIH HHS R00DE031148 to EYC
6 · The paper itself

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.

Indexed as

AchondroplasiaTyrosine Kinase InhibitorsAnimalsFemaleMaleMicePhenylurea CompoundsPyrimidinesRatsRats, WistarReceptors, Fibroblast Growth FactorX-Ray MicrotomographyinfigratinibPhenylurea CompoundsPyrimidinesReceptors, Fibroblast Growth FactorTyrosine Kinase Inhibitorsbonefibroblast growth factor receptormineralized tissue/developmenttooth development

Identifiers

PMID37435833
PMCPMC10784415
OpenAlexW4383998862

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.