Titel
Synthesis, Characterization andin vitroStudies of a Cathepsin B-Cleavable Prodrug of the VEGFR Inhibitor Sunitinib
Autor*in
Bettina Koblmüller
Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna
... show all
Abstract
Since several decades, the prodrug concept has raised considerable interest in cancer research due to its potential to overcome common problems associated with chemotherapy. However, for small‐molecule tyrosine kinase inhibitors, which also cause severe side effects, hardly any strategies to generate prodrugs for therapeutic improvement have been reported so far. Here, we present the synthesis and biological investigation of a cathepsin B‐cleavable prodrug of the VEGFR inhibitor sunitinib. Cell viability assays and Western blot analyses revealed, that, in contrast to the non‐cathepsin B‐cleavable reference compound, the prodrug shows activity comparable to the original drug sunitinib in the highly cathepsin B‐expressing cell lines Caki‐1 and RU‐MH. Moreover, a cathepsin B cleavage assay confirmed the desired enzymatic activation of the prodrug. Together, the obtained data show that the concept of cathepsin B‐cleavable prodrugs can be transferred to the class of targeted therapeutics, allowing the development of optimized tyrosine kinase inhibitors for the treatment of cancer.
Stichwort
tyrosine kinase inhibitorprodrugsinhibitorscathepsin Bsunitinibvascular endothelial growth
factor receptor (VEGFR)
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
phaidra.univie.ac.at/o:1095836
Erschienen in
Titel
Chemistry & Biodiversity
Band
16
Ausgabe
1
ISSN
1612-1872
Erscheinungsdatum
2018
Publication
Wiley
Fördergeber
Austrian Science Fund (FWF) — P28853
Erscheinungsdatum
2018
Zugänglichkeit
Rechte
Rechteangabe
© 2019 The Authors
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