doxorubicin prodrug L-377202

L-377202 is a peptide-conjugated prodrug of the anthracycline antibiotic doxorubicin, designed for selective activation in prostate cancer. The drug consists of a peptide covalently linked to doxorubicin; this complex is specifically hydrolyzed by prostate-specific antigen (PSA), an enzyme localized primarily to the prostate gland. Upon PSA-mediated cleavage, active metabolites—doxorubicin and leucine-doxorubicin—are released at the tumor site. These metabolites intercalate into DNA and inhibit type II DNA topoisomerase, thereby blocking DNA replication and repair as well as RNA and protein synthesis. They also generate toxic free radicals and induce lipid peroxidation in cell membranes. This targeted approach aims to maximize antitumor efficacy while minimizing systemic toxicity compared to conventional doxorubicin therapy[1][2][4][5][6].

Other names

doxorubicin prodrug L-377202Doxorubicin peptide conjugate - Merck