MITOMYCIN CONJUGATES CLEAVABLE BY THIOLS

摘要

Methods for administering mitomycin C to a multi-drug resistant cell and for reducing the toxicity of the compound are described. In the methods, mitomycin C is provided in the form of a prodrug conjugate, where the drug is linked to a hydrophobic moiety, such as a lipid, through a cleavable dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of mitomycin C in its original form. The linkage is stable under non reducing conditions. The prodrug conjugate can be incorporated into liposomes for administration in vivo reducing conditions or in response to administration of an exogenous reducing agent.