A Hydrogen Peroxide-Activatable Gemcitabine Prodrug for the Selective Treatment of Pancreatic Ductal Adenocarcinoma.

In this study, we aimed to decrease adverse events on gemcitabine (GEM) in the treatment of pancreatic ductal adenocarcinoma and focused on the difference of hydrogen peroxide (H2O2) levels in normal cells and cancer cells. We have designed and synthesized a novel boronate ester-caged prodrug that is activated by the high H2O2 concentration found in cancer cells to release GEM. An H2O2-activatable GEM (A-GEM) has higher selectivity for H2O2 over other ROS and cytotoxic effects corresponding to the H2O2 concentration in vitro. A xenograft model of immunodeficient mice indicated that the effect of A-GEM was not inferior to that of GEM, when administered in vivo. In particular, myelosuppression was significantly reduced following A-GEM treatment compared with that following GEM treatment.
PMID: 31207139 [PubMed - as supplied by publisher]

Source: ChemMedChem - June 16, 2019 Category: Chemistry Authors: Matsushita K, Okuda T, Mori S, Konno M, Eguchi H, Asai A, Koseki J, Iwagami Y, Yamada D, Akita H, Asaoka T, Noda T, Kawamoto K, Gotoh K, Kobayashi S, Kasahara Y, Morihiro K, Satoh T, Doki Y, Mori M, Ishii H, Obika S Tags: ChemMedChem Source Type: research