Aldoxorubicin is a prodrug form of the anthracycline antitumor antibiotic doxorubicin .1 Aldoxorubicin selectively binds to serum albumin, which releases doxorubicin in acidic environments, such as the tumor microenvironment. It inhibits the proliferation of RenCa renal cell carcinoma cells as well as MCF-7 breast and LXFL 529 lung cancer cells (IC50s = 1, 1.1, and 0.5 ?M, respectively). Aldoxorubicin (39.3 ?mol/kg) induces tumor regression in an MDA-MB-435 breast cancer mouse xenograft model. Unlike doxorubicin, aldoxorubicin is not toxic to mice (LD50 = >60 mg/kg).2 It has also been used to conjugate doxorubicin to antibodies.3
1.Kratz, F., Warnecke, A., Scheuermann, K., et al.Probing the cysteine-34 position of endogenous serum albumin with thiol-binding doxorubicin derivatives. Improved efficacy of an acid-sensitive doxorubicin derivative with specific albumin-binding properties compared to that of the parent compoundJ. Med. Chem.45(25)5523-5533(2002) 2.Kratz, F., Ehling, G., Kauffmann, H.M., et al.Acute and repeat-dose toxicity studies of the (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH), an albumin-binding prodrug of the anticancer agent doxorubicinHum. Exp. Toxicol.26(1)19-35(2007) 3.Willner, D., Trail, P.A., Hofstead, S.J., et al.(6-Maleimidocaproyl)hydrazone of doxorubicin—a new derivative for the preparation of immunoconjugates of doxorubicinBioconjug. Chem.4(6)521-527(1993)