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Acid-Sensitive Prodrugs of Doxorubicin

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Anthracycline Chemistry and Biology II

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 283))

Abstract

The endosomal and/or lysosomal pathway of macromolecules, as well as the slightly acidic extracellularenvironment in solid tumors, form the rationale for designing carrier-linked prodrugs with pH-dependentlinkers. In the past 20 years, a spectrum of acid-sensitive doxorubicin prodrugs has been developedwith antibodies, serum proteins, and synthetic polymers. For a number of these, a convincingproof of concept has been obtained preclinically, showing an enhanced therapeutic efficacy of theprodrugs compared to free doxorubicin in tumor models. Clinically, the (6-maleimidocaproyl)-hydrazonederivative of doxorubicin, which binds either to the monoclonal antibody BR96 or to endogenous albumin,has been evaluated in clinical trials.

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Authors and Affiliations

  1. Tumor Biology Center, Macromolecular Prodrugs, Breisacher Straße 117, 79106, Freiburg im Breisgau, Germany

    Felix Kratz

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  1. Felix Kratz
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Correspondence to Felix Kratz .

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Karsten Krohn

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© 2007 Springer-Verlag Berlin Heidelberg

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Kratz, F. (2007). Acid-Sensitive Prodrugs of Doxorubicin. In: Krohn, K. (eds) Anthracycline Chemistry and Biology II. Topics in Current Chemistry, vol 283. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2007_5

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