Authors
Paul Gueroue, Audrey Burban, Ahmad Sharanek, Guillaume Bougueon, Stéphane Bouchet, Dominique Ducint, Mathieu Molimard, Sarah Djabarouti, Joris Guyon
Published in
Scientific reports. Jun 24, 2026. Epub Jun 24, 2026.
Abstract
Owing to its involvement in extracellular matrix-glial cell interactions, discoidin domain receptor 2 (DDR2) has emerged as a promising pharmacological target in various human diseases, including cancers and neurodegenerative disorders. Two allosteric inhibitors, WRG-28 and DDR2-IN-1, selectively target DDR2. Their therapeutic efficacy is likely to depend on blood-brain barrier (BBB) penetration; however, a lack of analytical methods has so far left their pharmacokinetic properties and BBB permeability profiles largely unexplored. In this study, a liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of WRG-28 and DDR2-IN-1 in plasma and brain tissue. The extraction procedure was simple and based on protein precipitation followed by lipid removal. This analytical method met the acceptance criteria of the European Medicines Agency guidelines. The calibration range was linear from 1 to 1000 ng/mL for both compounds. In addition, five prediction software tools were used to estimate pharmacokinetic parameters relevant to the BBB penetration of the two compounds. Finally, the method was applied in preclinical pharmacokinetic studies using elacridar, an efflux transporter inhibitor.
PMID:
42342854
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.
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