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Updated: Sep 19, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs
Wolf Wrasidlo1, Ulrike Schröder, Kathrin Bernt
1Charité Children's Hospital, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. wrasidlo@charite.de
Abstract:
Two 4'-propylcarbonoxy derivatives (2,3) of etoposide (1), a topoisomerase II inhibitor, were synthesized and evaluated as potential prodrugs for anticancer therapy. Their activation via hydrolysis mechanisms was determined as a function of pH in buffer solutions, in human serum and in the presence of carboxyl ester hydrolase. Cytotoxicity was determined on various tumor cell lines and compared to the parent compound. On cell lines exhibiting resistance to etoposide we observed an enhanced cytotoxicity of the prodrugs of up to three orders of magnitude.
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