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Bone cancer

Cathepsin B

In vitro and mouse studies have identified a bone-targeting doxorubicin prodrug that could help treat bone metastasis. The prodrug contains a bone-targeting bisphosphonate ligand and an acid-sensitive or cathepsin B-cleavable linker to release doxorubicin specifically in bone. In binding assays, the prodrug specifically bound hydroxyapatite or native bone, had high plasma stability and released doxorubicin under acidic or cathepsin B-containing conditions. In mice, the maximum tolerable dose of the prodrug was three times higher than that of doxorubicin. Next steps could include testing the prodrug in bone metastasis models.

SciBX 5(37); doi:10.1038/scibx.2012.976
Published online Sept. 20, 2012

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Hochdörffer, K. et al. J. Med. Chem.; published online Aug. 13, 2012;
Contact: Felix Kratz, Tumor Biology Center, Freiburg, Germany